Mixed Topics

Despite being a targeted therapy, antibody-drug conjugates (ADCs) can cause significant off-target toxicity to the eyes of patients being treated for advanced multiple myeloma or cervical cancer, yet the risks remain relatively unknown, according to oncologists and ophthalmologists.

Such experts called for greater collaboration between oncologists and ophthalmologists, in interviews with Medscape Medical News.

ADCs combine a monoclonal antibody targeted at an antigen overexpressed on cancer cells with a toxic chemotherapy payload — the aim being to maximize the effectiveness of the drug against the tumor while minimizing the damage to healthy tissues and reducing systemic toxicity.

Yet trastuzumab duocarmazine (T-Duo), a third-generation human epidermal growth factor receptor 2 (HER2)–targeted ADC designed to treat HER2-positive breast cancer, was recently found to have a notable adverse effect in the TULIP trial of 437 patients.

As reported by Medscape Medical News, the drug was associated with a significant increase in progression-free survival over physician’s choice of therapy. However, 78% of patients in the ADC group experienced at least one treatment-emergent ocular toxicity adverse event vs 29.2% of those in the control group.

Moreover, grade 3 or high ocular toxicity events were reported by 21% of patients in the experimental group compared with none of those who received physician’s choice.

 

Ocular Toxicities Seen on Ocular Surface

Ocular toxicities with these drugs are “not necessarily a new thing,” said Joann J. Kang, MD, director, Cornea and Refractive Surgery, and associate professor of ophthalmology at Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

“But what we’re seeing with certain ADCs is a lot of ocular toxicity, especially on the ocular surface,” with the degree toxicity varying depending on the ADC in question. “It’s definitely a real concern.”

Kang noted that separate from T-Duo, certain ADCs already come with black box warnings for ocular toxicity, including:

• Belantamab mafodotin (Blenrep) — approved for relapsed or refractory multiple myeloma and carries a warning specifically for keratopathy.
• Tisotumab vedotin (Tivdak) — indicated for recurrent or metastatic cervical cancer and can cause changes in the corneal epithelium and conjunctiva.
• Mirvetuximab soravtansine (Elahere) — used to treat folate receptor (FR) alpha–positive ovarian, fallopian tube, and peritoneal cancers and can lead to keratopathy, blurred vision, and dry eyes.

Indeed, the American Academy of Ophthalmology 2024 annual meeting saw research presented indicating that mirvetuximab was associated with moderate or severe corneal toxicity in 47% of patients treated for primary gynecologic malignancies.

As reported by Medscape Medical News, the study, by researchers at Byers Eye Institute of Stanford University in Stanford, California, was a retrospective analysis of 36 eyes of 18 women who received mirvetuximab for FR alpha–positive, platinum-resistant primary ovarian cancer.

 

What Are the Causes?

But why would a drug that is targeted specifically to a cancer tumor, thanks to the presence of a monoclonal antibody, cause off-target effects such as ocular toxicity?

Kathy D. Miller, MD, professor of oncology and medicine at Indiana University School of Medicine in Indianapolis, pointed out that they are targeted in a relative and not absolute sense, meaning that the antigen target may not be truly limited to the tumor cells.

There can also be “a lot of ways that you could get systemic toxicities,” she said.

For example, if the linker connecting the antibody and the chemotherapy payload breaks prematurely or is not stable, or if the drug leaches out into the tumor microenvironment and then is “picked up into the circulation, that can give you systemic toxicity,” she said.

In addition, the drug may, once it is in the tumor cells, be metabolized to an active metabolite that could, again, result in systemic exposure.

 

Side Effects Are Underappreciated and Distressing

Ocular toxicity remains underappreciated among oncologists prescribing these drugs. One reason is that it “did not get enough attention” in the initial clinical trial reports, Miller said she suspects.

Another potential reason for this is that “we’re not used to thinking about it because it’s not particularly common among the drugs that oncologists use frequently,” she added. Additionally, it tends to come up later during treatment, “so people have to be on therapy for some time before you start to see it.”

Nevertheless, Miller underlined that ocular toxicity “can be particularly distressing for patients, as it’s uncomfortable [and] can lead to scarring, so some of the vision issues can be permanent.”

“We often see in these situations that there are different types of ocular toxicities that present in different patients,” said Jane L. Meisel, MD, co-director, Breast Medical Oncology, Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

“Corneal damage is pretty common, and patients can present with blurry vision, or dry eyes, or light sensitivity. And unlike some side effects, these are things that really impact people at every waking moment of their day.”

“So they’re pretty clinically significant side effects, even if they’re not life-threatening,” Meisel emphasized.

Miller suspects that more heavily pretreated patients may be more likely to experience ocular toxicity, as “there’s a much higher incidence of dry eyes in our patients than we recognize.”

She added: “We don’t usually ask about it, and we certainly don’t routinely do Schirmer’s tests,” which determine whether the eye produces enough tears to keep it moist.

 

Preventive Measures

For patients receiving tisotumab or mirvetuximab who experience ocular toxicity, Kang said the recommendation is to use steroid eye drops before, during, and after treatment with the ADC.

However, she noted that steroids have not been found to be useful in patients given belantamab, so clinicians have tried vasoconstrictor eye drops immediately prior to the infusion, as well as ocular cooling masks, which “are thought to help by reducing blood supply to the ocular areas.”

Other approaches to minimize ocular toxicity have included longer infusion times, so it’s “not so much of a hefty dose at one time,” Kang added.

She underlined that grade 2 and 3 ocular toxicities can lead to dose delays or dose modifications, and “usually by the time you get a grade 4 event, then you may need to discontinue the medication.”

This can have consequences for the patients because they are often “very sick, and this may be their third agent that they’re trying,” or it may be that their tumor is responding to a new treatment, but it has to be withheld because of an ocular toxicity.

“It can be incredibly frustrating for patients, and also for oncologists, and then for ophthalmologists,” Kang said.

 

Closer Collaboration Between Specialists Needed

What’s known about ocular side effects in patients taking ADCs underlines that there is a need for closer collaboration between oncologists and ophthalmologists.

“In oncology, especially as immunotherapies came to the forefront, our relationships with our endocrinology colleagues have become stronger because we’ve needed them to help us manage things like thyroid toxicity and pituitary issues related to immunotherapy,” Meisel said.

With toxicities that may be “very impactful for patient quality of life, like ocular toxicity, we will need to learn more about them and develop protocols for management, along with our ophthalmology colleagues, so that we can keep patients as comfortable as possible, while maximizing the efficacy of these drugs.”

Miller agreed, saying oncologists need to have “a conversation with a local ophthalmologist,” although she conceded that, in many areas, such specialists “are in short supply.”

The oncologist “not only needs to be aware” of and looking for ocular toxicity when using these ADCs but also needs to be thinking: “If I run into trouble here, who’s my ophthalmology backup? Are they familiar with this drug? And do we have a plan for the multispecialty management of patients who run into this toxicity?”

 

Setting Counts When Assessing Toxicities

But do all these considerations mean that ADCs’ potential ocular toxicity should give clinicians pause when considering whether to use these drugs?

“What my patients most want are drugs that work; that are effective in controlling their tumors,” Miller said.

“Every drug we use has potential toxicities, and which toxicities are most physically troublesome [or] are the greatest concern may vary from patient to patient, and it may vary a lot from patients with metastatic disease to those in the curative setting.”

She explained that “toxicities that might not be prohibitive at all in the metastatic setting [may] have to be a much bigger part of our considerations” when moving drugs into the adjuvant or neoadjuvant setting.

This, Miller underlined, is where the ocular toxicity with these ADCs “may be much more prohibitive.”

TULIP was funded by Byondis BV.

Turner declared relationships with Novartis, AstraZeneca, Pfizer, Merck Sharp & Dohme, Lilly, Repare Therapeutics, Roche, GlaxoSmithKline, Gilead Sciences, Inivata, Guardant Health, Exact Sciences, and Relay Therapeutics.

Meisel declared relationships with Novartis, AstraZeneca, Genentech, Seagen, Olema Oncology, GE Healthcare, Pfizer, Stemline, and Sermonix Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

Despite being a targeted therapy, antibody-drug conjugates (ADCs) can cause significant off-target toxicity to the eyes of patients being treated for advanced multiple myeloma or cervical cancer, yet the risks remain relatively unknown, according to oncologists and ophthalmologists.

Such experts called for greater collaboration between oncologists and ophthalmologists, in interviews with Medscape Medical News.

ADCs combine a monoclonal antibody targeted at an antigen overexpressed on cancer cells with a toxic chemotherapy payload — the aim being to maximize the effectiveness of the drug against the tumor while minimizing the damage to healthy tissues and reducing systemic toxicity.

Yet trastuzumab duocarmazine (T-Duo), a third-generation human epidermal growth factor receptor 2 (HER2)–targeted ADC designed to treat HER2-positive breast cancer, was recently found to have a notable adverse effect in the TULIP trial of 437 patients.

As reported by Medscape Medical News, the drug was associated with a significant increase in progression-free survival over physician’s choice of therapy. However, 78% of patients in the ADC group experienced at least one treatment-emergent ocular toxicity adverse event vs 29.2% of those in the control group.

Moreover, grade 3 or high ocular toxicity events were reported by 21% of patients in the experimental group compared with none of those who received physician’s choice.

 

Ocular Toxicities Seen on Ocular Surface

Ocular toxicities with these drugs are “not necessarily a new thing,” said Joann J. Kang, MD, director, Cornea and Refractive Surgery, and associate professor of ophthalmology at Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

“But what we’re seeing with certain ADCs is a lot of ocular toxicity, especially on the ocular surface,” with the degree toxicity varying depending on the ADC in question. “It’s definitely a real concern.”

Kang noted that separate from T-Duo, certain ADCs already come with black box warnings for ocular toxicity, including:

• Belantamab mafodotin (Blenrep) — approved for relapsed or refractory multiple myeloma and carries a warning specifically for keratopathy.
• Tisotumab vedotin (Tivdak) — indicated for recurrent or metastatic cervical cancer and can cause changes in the corneal epithelium and conjunctiva.
• Mirvetuximab soravtansine (Elahere) — used to treat folate receptor (FR) alpha–positive ovarian, fallopian tube, and peritoneal cancers and can lead to keratopathy, blurred vision, and dry eyes.

Indeed, the American Academy of Ophthalmology 2024 annual meeting saw research presented indicating that mirvetuximab was associated with moderate or severe corneal toxicity in 47% of patients treated for primary gynecologic malignancies.

As reported by Medscape Medical News, the study, by researchers at Byers Eye Institute of Stanford University in Stanford, California, was a retrospective analysis of 36 eyes of 18 women who received mirvetuximab for FR alpha–positive, platinum-resistant primary ovarian cancer.

 

What Are the Causes?

But why would a drug that is targeted specifically to a cancer tumor, thanks to the presence of a monoclonal antibody, cause off-target effects such as ocular toxicity?

Kathy D. Miller, MD, professor of oncology and medicine at Indiana University School of Medicine in Indianapolis, pointed out that they are targeted in a relative and not absolute sense, meaning that the antigen target may not be truly limited to the tumor cells.

There can also be “a lot of ways that you could get systemic toxicities,” she said.

For example, if the linker connecting the antibody and the chemotherapy payload breaks prematurely or is not stable, or if the drug leaches out into the tumor microenvironment and then is “picked up into the circulation, that can give you systemic toxicity,” she said.

In addition, the drug may, once it is in the tumor cells, be metabolized to an active metabolite that could, again, result in systemic exposure.

 

Side Effects Are Underappreciated and Distressing

Ocular toxicity remains underappreciated among oncologists prescribing these drugs. One reason is that it “did not get enough attention” in the initial clinical trial reports, Miller said she suspects.

Another potential reason for this is that “we’re not used to thinking about it because it’s not particularly common among the drugs that oncologists use frequently,” she added. Additionally, it tends to come up later during treatment, “so people have to be on therapy for some time before you start to see it.”

Nevertheless, Miller underlined that ocular toxicity “can be particularly distressing for patients, as it’s uncomfortable [and] can lead to scarring, so some of the vision issues can be permanent.”

“We often see in these situations that there are different types of ocular toxicities that present in different patients,” said Jane L. Meisel, MD, co-director, Breast Medical Oncology, Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

“Corneal damage is pretty common, and patients can present with blurry vision, or dry eyes, or light sensitivity. And unlike some side effects, these are things that really impact people at every waking moment of their day.”

“So they’re pretty clinically significant side effects, even if they’re not life-threatening,” Meisel emphasized.

Miller suspects that more heavily pretreated patients may be more likely to experience ocular toxicity, as “there’s a much higher incidence of dry eyes in our patients than we recognize.”

She added: “We don’t usually ask about it, and we certainly don’t routinely do Schirmer’s tests,” which determine whether the eye produces enough tears to keep it moist.

 

Preventive Measures

For patients receiving tisotumab or mirvetuximab who experience ocular toxicity, Kang said the recommendation is to use steroid eye drops before, during, and after treatment with the ADC.

However, she noted that steroids have not been found to be useful in patients given belantamab, so clinicians have tried vasoconstrictor eye drops immediately prior to the infusion, as well as ocular cooling masks, which “are thought to help by reducing blood supply to the ocular areas.”

Other approaches to minimize ocular toxicity have included longer infusion times, so it’s “not so much of a hefty dose at one time,” Kang added.

She underlined that grade 2 and 3 ocular toxicities can lead to dose delays or dose modifications, and “usually by the time you get a grade 4 event, then you may need to discontinue the medication.”

This can have consequences for the patients because they are often “very sick, and this may be their third agent that they’re trying,” or it may be that their tumor is responding to a new treatment, but it has to be withheld because of an ocular toxicity.

“It can be incredibly frustrating for patients, and also for oncologists, and then for ophthalmologists,” Kang said.

 

Closer Collaboration Between Specialists Needed

What’s known about ocular side effects in patients taking ADCs underlines that there is a need for closer collaboration between oncologists and ophthalmologists.

“In oncology, especially as immunotherapies came to the forefront, our relationships with our endocrinology colleagues have become stronger because we’ve needed them to help us manage things like thyroid toxicity and pituitary issues related to immunotherapy,” Meisel said.

With toxicities that may be “very impactful for patient quality of life, like ocular toxicity, we will need to learn more about them and develop protocols for management, along with our ophthalmology colleagues, so that we can keep patients as comfortable as possible, while maximizing the efficacy of these drugs.”

Miller agreed, saying oncologists need to have “a conversation with a local ophthalmologist,” although she conceded that, in many areas, such specialists “are in short supply.”

The oncologist “not only needs to be aware” of and looking for ocular toxicity when using these ADCs but also needs to be thinking: “If I run into trouble here, who’s my ophthalmology backup? Are they familiar with this drug? And do we have a plan for the multispecialty management of patients who run into this toxicity?”

 

Setting Counts When Assessing Toxicities

But do all these considerations mean that ADCs’ potential ocular toxicity should give clinicians pause when considering whether to use these drugs?

“What my patients most want are drugs that work; that are effective in controlling their tumors,” Miller said.

“Every drug we use has potential toxicities, and which toxicities are most physically troublesome [or] are the greatest concern may vary from patient to patient, and it may vary a lot from patients with metastatic disease to those in the curative setting.”

She explained that “toxicities that might not be prohibitive at all in the metastatic setting [may] have to be a much bigger part of our considerations” when moving drugs into the adjuvant or neoadjuvant setting.

This, Miller underlined, is where the ocular toxicity with these ADCs “may be much more prohibitive.”

TULIP was funded by Byondis BV.

Turner declared relationships with Novartis, AstraZeneca, Pfizer, Merck Sharp & Dohme, Lilly, Repare Therapeutics, Roche, GlaxoSmithKline, Gilead Sciences, Inivata, Guardant Health, Exact Sciences, and Relay Therapeutics.

Meisel declared relationships with Novartis, AstraZeneca, Genentech, Seagen, Olema Oncology, GE Healthcare, Pfizer, Stemline, and Sermonix Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

Despite being a targeted therapy, antibody-drug conjugates (ADCs) can cause significant off-target toxicity to the eyes of patients being treated for advanced multiple myeloma or cervical cancer, yet the risks remain relatively unknown, according to oncologists and ophthalmologists.

Such experts called for greater collaboration between oncologists and ophthalmologists, in interviews with Medscape Medical News.

ADCs combine a monoclonal antibody targeted at an antigen overexpressed on cancer cells with a toxic chemotherapy payload — the aim being to maximize the effectiveness of the drug against the tumor while minimizing the damage to healthy tissues and reducing systemic toxicity.

Yet trastuzumab duocarmazine (T-Duo), a third-generation human epidermal growth factor receptor 2 (HER2)–targeted ADC designed to treat HER2-positive breast cancer, was recently found to have a notable adverse effect in the TULIP trial of 437 patients.

As reported by Medscape Medical News, the drug was associated with a significant increase in progression-free survival over physician’s choice of therapy. However, 78% of patients in the ADC group experienced at least one treatment-emergent ocular toxicity adverse event vs 29.2% of those in the control group.

Moreover, grade 3 or high ocular toxicity events were reported by 21% of patients in the experimental group compared with none of those who received physician’s choice.

 

Ocular Toxicities Seen on Ocular Surface

Ocular toxicities with these drugs are “not necessarily a new thing,” said Joann J. Kang, MD, director, Cornea and Refractive Surgery, and associate professor of ophthalmology at Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, New York.

“But what we’re seeing with certain ADCs is a lot of ocular toxicity, especially on the ocular surface,” with the degree toxicity varying depending on the ADC in question. “It’s definitely a real concern.”

Kang noted that separate from T-Duo, certain ADCs already come with black box warnings for ocular toxicity, including:

• Belantamab mafodotin (Blenrep) — approved for relapsed or refractory multiple myeloma and carries a warning specifically for keratopathy.
• Tisotumab vedotin (Tivdak) — indicated for recurrent or metastatic cervical cancer and can cause changes in the corneal epithelium and conjunctiva.
• Mirvetuximab soravtansine (Elahere) — used to treat folate receptor (FR) alpha–positive ovarian, fallopian tube, and peritoneal cancers and can lead to keratopathy, blurred vision, and dry eyes.

Indeed, the American Academy of Ophthalmology 2024 annual meeting saw research presented indicating that mirvetuximab was associated with moderate or severe corneal toxicity in 47% of patients treated for primary gynecologic malignancies.

As reported by Medscape Medical News, the study, by researchers at Byers Eye Institute of Stanford University in Stanford, California, was a retrospective analysis of 36 eyes of 18 women who received mirvetuximab for FR alpha–positive, platinum-resistant primary ovarian cancer.

 

What Are the Causes?

But why would a drug that is targeted specifically to a cancer tumor, thanks to the presence of a monoclonal antibody, cause off-target effects such as ocular toxicity?

Kathy D. Miller, MD, professor of oncology and medicine at Indiana University School of Medicine in Indianapolis, pointed out that they are targeted in a relative and not absolute sense, meaning that the antigen target may not be truly limited to the tumor cells.

There can also be “a lot of ways that you could get systemic toxicities,” she said.

For example, if the linker connecting the antibody and the chemotherapy payload breaks prematurely or is not stable, or if the drug leaches out into the tumor microenvironment and then is “picked up into the circulation, that can give you systemic toxicity,” she said.

In addition, the drug may, once it is in the tumor cells, be metabolized to an active metabolite that could, again, result in systemic exposure.

 

Side Effects Are Underappreciated and Distressing

Ocular toxicity remains underappreciated among oncologists prescribing these drugs. One reason is that it “did not get enough attention” in the initial clinical trial reports, Miller said she suspects.

Another potential reason for this is that “we’re not used to thinking about it because it’s not particularly common among the drugs that oncologists use frequently,” she added. Additionally, it tends to come up later during treatment, “so people have to be on therapy for some time before you start to see it.”

Nevertheless, Miller underlined that ocular toxicity “can be particularly distressing for patients, as it’s uncomfortable [and] can lead to scarring, so some of the vision issues can be permanent.”

“We often see in these situations that there are different types of ocular toxicities that present in different patients,” said Jane L. Meisel, MD, co-director, Breast Medical Oncology, Department of Hematology and Medical Oncology at Emory University School of Medicine in Atlanta.

“Corneal damage is pretty common, and patients can present with blurry vision, or dry eyes, or light sensitivity. And unlike some side effects, these are things that really impact people at every waking moment of their day.”

“So they’re pretty clinically significant side effects, even if they’re not life-threatening,” Meisel emphasized.

Miller suspects that more heavily pretreated patients may be more likely to experience ocular toxicity, as “there’s a much higher incidence of dry eyes in our patients than we recognize.”

She added: “We don’t usually ask about it, and we certainly don’t routinely do Schirmer’s tests,” which determine whether the eye produces enough tears to keep it moist.

 

Preventive Measures

For patients receiving tisotumab or mirvetuximab who experience ocular toxicity, Kang said the recommendation is to use steroid eye drops before, during, and after treatment with the ADC.

However, she noted that steroids have not been found to be useful in patients given belantamab, so clinicians have tried vasoconstrictor eye drops immediately prior to the infusion, as well as ocular cooling masks, which “are thought to help by reducing blood supply to the ocular areas.”

Other approaches to minimize ocular toxicity have included longer infusion times, so it’s “not so much of a hefty dose at one time,” Kang added.

She underlined that grade 2 and 3 ocular toxicities can lead to dose delays or dose modifications, and “usually by the time you get a grade 4 event, then you may need to discontinue the medication.”

This can have consequences for the patients because they are often “very sick, and this may be their third agent that they’re trying,” or it may be that their tumor is responding to a new treatment, but it has to be withheld because of an ocular toxicity.

“It can be incredibly frustrating for patients, and also for oncologists, and then for ophthalmologists,” Kang said.

 

Closer Collaboration Between Specialists Needed

What’s known about ocular side effects in patients taking ADCs underlines that there is a need for closer collaboration between oncologists and ophthalmologists.

“In oncology, especially as immunotherapies came to the forefront, our relationships with our endocrinology colleagues have become stronger because we’ve needed them to help us manage things like thyroid toxicity and pituitary issues related to immunotherapy,” Meisel said.

With toxicities that may be “very impactful for patient quality of life, like ocular toxicity, we will need to learn more about them and develop protocols for management, along with our ophthalmology colleagues, so that we can keep patients as comfortable as possible, while maximizing the efficacy of these drugs.”

Miller agreed, saying oncologists need to have “a conversation with a local ophthalmologist,” although she conceded that, in many areas, such specialists “are in short supply.”

The oncologist “not only needs to be aware” of and looking for ocular toxicity when using these ADCs but also needs to be thinking: “If I run into trouble here, who’s my ophthalmology backup? Are they familiar with this drug? And do we have a plan for the multispecialty management of patients who run into this toxicity?”

 

Setting Counts When Assessing Toxicities

But do all these considerations mean that ADCs’ potential ocular toxicity should give clinicians pause when considering whether to use these drugs?

“What my patients most want are drugs that work; that are effective in controlling their tumors,” Miller said.

“Every drug we use has potential toxicities, and which toxicities are most physically troublesome [or] are the greatest concern may vary from patient to patient, and it may vary a lot from patients with metastatic disease to those in the curative setting.”

She explained that “toxicities that might not be prohibitive at all in the metastatic setting [may] have to be a much bigger part of our considerations” when moving drugs into the adjuvant or neoadjuvant setting.

This, Miller underlined, is where the ocular toxicity with these ADCs “may be much more prohibitive.”

TULIP was funded by Byondis BV.

Turner declared relationships with Novartis, AstraZeneca, Pfizer, Merck Sharp & Dohme, Lilly, Repare Therapeutics, Roche, GlaxoSmithKline, Gilead Sciences, Inivata, Guardant Health, Exact Sciences, and Relay Therapeutics.

Meisel declared relationships with Novartis, AstraZeneca, Genentech, Seagen, Olema Oncology, GE Healthcare, Pfizer, Stemline, and Sermonix Pharmaceuticals.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

Working as an emergency physician can be demanding. It’s also dangerous. In a 2022 study, two thirds of emergency physicians were assaulted in the past 12 months, and one third of those assaults resulted in an injury.

The attacks included verbal assaults with threats of violence (64%), hits/slaps (40%), being spit on (31%), kicked (26%), and punched (25%). Nearly one in four physicians said they were assaulted multiple times. 

The same survey found that 85% of emergency physicians believe that violence in the emergency department (ED) has increased over the past 5 years; nearly half (45%) say it has greatly increased.

To offset this disturbing trend, healthcare systems are trying new measures to reduce or prevent violence in the ED and protect staff and patients. EDs have security cameras, metal detectors, panic alarms, and security guards. And now more security guards are using body-worn cameras (bodycams) like police wear, to protect ED doctors and staff.

 

Bodycams in the ED

Scott Hill, EdD, CPP, CHPA, a board member of the International Association for Healthcare Security and Safety Foundation, recently published a study on the impact of hospital security officers using bodycams. The study surveyed more than 100 hospitals. Fifty-three had security guards wearing bodycams; 57 had security guards without them.

The study supported the benefits of implementing body-worn cameras in a healthcare environment, said Hill, the former director of safety and security for King’s Daughters Health System in Ashland, Kentucky. “We were a little surprised by the data, but basically there was a positive impact…on the safety of hospital staff. There was higher officer confidence, better record-keeping, improved customer service, better training ... and better protection from false allegations.”

Hill told Medscape Medical News that bodycams can make for a safer ED. “The body-worn camera group believed that the cameras would have a positive impact that would make patients and staff feel safer,” said Hill. The idea is that security guards will use force more appropriately because the bodycam provides protection from false accusations.

Appropriate, timely intervention with disruptive or violent patients (or their family members) creates a safer environment for doctors, nurses, and other staff. (While the study found that hospital personnel felt safer with security guards wearing bodycams, physicians and healthcare staff were not surveyed in the study.)

 

Should Doctors Wear Bodycams?

While the idea of ED physicians or nurses wearing bodycams has been suggested, it’s a novel one to Jeffrey Goodloe, MD, an emergency physician in Tulsa, Oklahoma, and member of the American College of Emergency Physicians’ board of directors. “Even with a very vast network of colleagues, both professional and personal friends…I am personally not aware of an ER physician who wears a bodycam,” said Goodloe.

However, there’s no consensus on whether they should, he added. “If you ask 10 emergency room physicians [about wearing bodycams], some will say, ‘That would help’; some would say, ‘from an academic perspective, we don’t have the data,’ some would say, ‘what about privacy concerns?’ You’ll get all those responses,” said Goodloe.

“If a doctor is wearing a bodycam, one of the risks is that patients may not want to be upfront because they see a camera and they see it’s being recorded,” said Edward Wright, MD, a board-certified emergency medicine physician who owns freestanding emergency rooms (ERs) in San Antonio. “It could cause a lot of damage to the relationship between the patient and the physician.”

 

Other Potential Drawbacks of Bodycams

When it comes to patient care, “the presence of a body camera [on a security guard] in and of itself is not intrusive or detrimental to the professional actions of an emergency physician,” said Goodloe, who often sees police officers and security guards with bodycams in the ED. “However, when we are in the process of treating patients, there is a certain amount of privacy that patients and their families and loved ones have a reasonable right to expect in an ED.”

Wright has seen police officers wearing body cameras as well as patients using their phones to record in the ED. “That happens a lot…in Texas, anyone in a public place can record audio and video,” said Wright. “I would say the concern with anyone recording things is patient’s privacy and HIPPA concerns.” While some areas, like the waiting room and hallways, are considered public, the patient care areas are typically private — and a bodycam could violate that privacy.

“The biggest concern we have with bodycams is the unintended violation of someone else’s privacy,” said Goodloe. In an ER setting, he explains that it’s difficult for someone wearing a bodycam to prevent unintentionally recording multiple other patients in the footage. “How do we provide care and protect patient privacy?”

And while a camera makes a record, it may not always be an accurate reflection of what happened. “You might have a video record of what I said and what the patient said, but the camera doesn’t tell the whole story,” said Wright. “There are nuances, and there may be family members who are not on camera…you have to consider that something may be missing.”

Most EDs have wall-mounted security cameras; a 2023 study found that 94.7% had security cameras in key locations. Signage alerting patients of cameras is also common; more than half of EDs have signage warning patients and visitors that they are being recorded, so there may be little expectation of privacy in public areas. But unfortunately, sometimes, patients must be triaged, and treated, in the hallways of busy EDs, where they are subject to being recorded either on stationary or body-worn cameras.

 

Keeping the ED Safe

Putting aside privacy concerns, security measures meant to protect staff and patients can only do so much. “Some security measures are more of a feel-good measure,” said Wright. “We have automatic door locks for our doors, but the whole side of the building is glass…my personal feeling is that cameras can be a deterrent, but if someone has an intention to hurt someone else or is psychotic, you aren’t going to be able to stop them from what they’re going to do.”

Regardless, we’re likely to see more security measures like body-worn cameras in the ED. “Workplace safety is very much on the minds of ER physicians and ER nurses,” said Goodloe. “EDs have become sites of workplace violence with unacceptable increasing frequency…how do we solve this, [while] simultaneously not discouraging or preventing access to emergency care when and where people need it most?”

“We truly care about patient safety and our colleagues’ safety, and we want to be able to come in and make a positive difference,” said Goodloe. But ultimately, doctors want to go home safely to their families, and they want their patients to be able to do that, too.

 

A version of this article appeared on Medscape.com.

Working as an emergency physician can be demanding. It’s also dangerous. In a 2022 study, two thirds of emergency physicians were assaulted in the past 12 months, and one third of those assaults resulted in an injury.

The attacks included verbal assaults with threats of violence (64%), hits/slaps (40%), being spit on (31%), kicked (26%), and punched (25%). Nearly one in four physicians said they were assaulted multiple times. 

The same survey found that 85% of emergency physicians believe that violence in the emergency department (ED) has increased over the past 5 years; nearly half (45%) say it has greatly increased.

To offset this disturbing trend, healthcare systems are trying new measures to reduce or prevent violence in the ED and protect staff and patients. EDs have security cameras, metal detectors, panic alarms, and security guards. And now more security guards are using body-worn cameras (bodycams) like police wear, to protect ED doctors and staff.

 

Bodycams in the ED

Scott Hill, EdD, CPP, CHPA, a board member of the International Association for Healthcare Security and Safety Foundation, recently published a study on the impact of hospital security officers using bodycams. The study surveyed more than 100 hospitals. Fifty-three had security guards wearing bodycams; 57 had security guards without them.

The study supported the benefits of implementing body-worn cameras in a healthcare environment, said Hill, the former director of safety and security for King’s Daughters Health System in Ashland, Kentucky. “We were a little surprised by the data, but basically there was a positive impact…on the safety of hospital staff. There was higher officer confidence, better record-keeping, improved customer service, better training ... and better protection from false allegations.”

Hill told Medscape Medical News that bodycams can make for a safer ED. “The body-worn camera group believed that the cameras would have a positive impact that would make patients and staff feel safer,” said Hill. The idea is that security guards will use force more appropriately because the bodycam provides protection from false accusations.

Appropriate, timely intervention with disruptive or violent patients (or their family members) creates a safer environment for doctors, nurses, and other staff. (While the study found that hospital personnel felt safer with security guards wearing bodycams, physicians and healthcare staff were not surveyed in the study.)

 

Should Doctors Wear Bodycams?

While the idea of ED physicians or nurses wearing bodycams has been suggested, it’s a novel one to Jeffrey Goodloe, MD, an emergency physician in Tulsa, Oklahoma, and member of the American College of Emergency Physicians’ board of directors. “Even with a very vast network of colleagues, both professional and personal friends…I am personally not aware of an ER physician who wears a bodycam,” said Goodloe.

However, there’s no consensus on whether they should, he added. “If you ask 10 emergency room physicians [about wearing bodycams], some will say, ‘That would help’; some would say, ‘from an academic perspective, we don’t have the data,’ some would say, ‘what about privacy concerns?’ You’ll get all those responses,” said Goodloe.

“If a doctor is wearing a bodycam, one of the risks is that patients may not want to be upfront because they see a camera and they see it’s being recorded,” said Edward Wright, MD, a board-certified emergency medicine physician who owns freestanding emergency rooms (ERs) in San Antonio. “It could cause a lot of damage to the relationship between the patient and the physician.”

 

Other Potential Drawbacks of Bodycams

When it comes to patient care, “the presence of a body camera [on a security guard] in and of itself is not intrusive or detrimental to the professional actions of an emergency physician,” said Goodloe, who often sees police officers and security guards with bodycams in the ED. “However, when we are in the process of treating patients, there is a certain amount of privacy that patients and their families and loved ones have a reasonable right to expect in an ED.”

Wright has seen police officers wearing body cameras as well as patients using their phones to record in the ED. “That happens a lot…in Texas, anyone in a public place can record audio and video,” said Wright. “I would say the concern with anyone recording things is patient’s privacy and HIPPA concerns.” While some areas, like the waiting room and hallways, are considered public, the patient care areas are typically private — and a bodycam could violate that privacy.

“The biggest concern we have with bodycams is the unintended violation of someone else’s privacy,” said Goodloe. In an ER setting, he explains that it’s difficult for someone wearing a bodycam to prevent unintentionally recording multiple other patients in the footage. “How do we provide care and protect patient privacy?”

And while a camera makes a record, it may not always be an accurate reflection of what happened. “You might have a video record of what I said and what the patient said, but the camera doesn’t tell the whole story,” said Wright. “There are nuances, and there may be family members who are not on camera…you have to consider that something may be missing.”

Most EDs have wall-mounted security cameras; a 2023 study found that 94.7% had security cameras in key locations. Signage alerting patients of cameras is also common; more than half of EDs have signage warning patients and visitors that they are being recorded, so there may be little expectation of privacy in public areas. But unfortunately, sometimes, patients must be triaged, and treated, in the hallways of busy EDs, where they are subject to being recorded either on stationary or body-worn cameras.

 

Keeping the ED Safe

Putting aside privacy concerns, security measures meant to protect staff and patients can only do so much. “Some security measures are more of a feel-good measure,” said Wright. “We have automatic door locks for our doors, but the whole side of the building is glass…my personal feeling is that cameras can be a deterrent, but if someone has an intention to hurt someone else or is psychotic, you aren’t going to be able to stop them from what they’re going to do.”

Regardless, we’re likely to see more security measures like body-worn cameras in the ED. “Workplace safety is very much on the minds of ER physicians and ER nurses,” said Goodloe. “EDs have become sites of workplace violence with unacceptable increasing frequency…how do we solve this, [while] simultaneously not discouraging or preventing access to emergency care when and where people need it most?”

“We truly care about patient safety and our colleagues’ safety, and we want to be able to come in and make a positive difference,” said Goodloe. But ultimately, doctors want to go home safely to their families, and they want their patients to be able to do that, too.

 

A version of this article appeared on Medscape.com.

Working as an emergency physician can be demanding. It’s also dangerous. In a 2022 study, two thirds of emergency physicians were assaulted in the past 12 months, and one third of those assaults resulted in an injury.

The attacks included verbal assaults with threats of violence (64%), hits/slaps (40%), being spit on (31%), kicked (26%), and punched (25%). Nearly one in four physicians said they were assaulted multiple times. 

The same survey found that 85% of emergency physicians believe that violence in the emergency department (ED) has increased over the past 5 years; nearly half (45%) say it has greatly increased.

To offset this disturbing trend, healthcare systems are trying new measures to reduce or prevent violence in the ED and protect staff and patients. EDs have security cameras, metal detectors, panic alarms, and security guards. And now more security guards are using body-worn cameras (bodycams) like police wear, to protect ED doctors and staff.

 

Bodycams in the ED

Scott Hill, EdD, CPP, CHPA, a board member of the International Association for Healthcare Security and Safety Foundation, recently published a study on the impact of hospital security officers using bodycams. The study surveyed more than 100 hospitals. Fifty-three had security guards wearing bodycams; 57 had security guards without them.

The study supported the benefits of implementing body-worn cameras in a healthcare environment, said Hill, the former director of safety and security for King’s Daughters Health System in Ashland, Kentucky. “We were a little surprised by the data, but basically there was a positive impact…on the safety of hospital staff. There was higher officer confidence, better record-keeping, improved customer service, better training ... and better protection from false allegations.”

Hill told Medscape Medical News that bodycams can make for a safer ED. “The body-worn camera group believed that the cameras would have a positive impact that would make patients and staff feel safer,” said Hill. The idea is that security guards will use force more appropriately because the bodycam provides protection from false accusations.

Appropriate, timely intervention with disruptive or violent patients (or their family members) creates a safer environment for doctors, nurses, and other staff. (While the study found that hospital personnel felt safer with security guards wearing bodycams, physicians and healthcare staff were not surveyed in the study.)

 

Should Doctors Wear Bodycams?

While the idea of ED physicians or nurses wearing bodycams has been suggested, it’s a novel one to Jeffrey Goodloe, MD, an emergency physician in Tulsa, Oklahoma, and member of the American College of Emergency Physicians’ board of directors. “Even with a very vast network of colleagues, both professional and personal friends…I am personally not aware of an ER physician who wears a bodycam,” said Goodloe.

However, there’s no consensus on whether they should, he added. “If you ask 10 emergency room physicians [about wearing bodycams], some will say, ‘That would help’; some would say, ‘from an academic perspective, we don’t have the data,’ some would say, ‘what about privacy concerns?’ You’ll get all those responses,” said Goodloe.

“If a doctor is wearing a bodycam, one of the risks is that patients may not want to be upfront because they see a camera and they see it’s being recorded,” said Edward Wright, MD, a board-certified emergency medicine physician who owns freestanding emergency rooms (ERs) in San Antonio. “It could cause a lot of damage to the relationship between the patient and the physician.”

 

Other Potential Drawbacks of Bodycams

When it comes to patient care, “the presence of a body camera [on a security guard] in and of itself is not intrusive or detrimental to the professional actions of an emergency physician,” said Goodloe, who often sees police officers and security guards with bodycams in the ED. “However, when we are in the process of treating patients, there is a certain amount of privacy that patients and their families and loved ones have a reasonable right to expect in an ED.”

Wright has seen police officers wearing body cameras as well as patients using their phones to record in the ED. “That happens a lot…in Texas, anyone in a public place can record audio and video,” said Wright. “I would say the concern with anyone recording things is patient’s privacy and HIPPA concerns.” While some areas, like the waiting room and hallways, are considered public, the patient care areas are typically private — and a bodycam could violate that privacy.

“The biggest concern we have with bodycams is the unintended violation of someone else’s privacy,” said Goodloe. In an ER setting, he explains that it’s difficult for someone wearing a bodycam to prevent unintentionally recording multiple other patients in the footage. “How do we provide care and protect patient privacy?”

And while a camera makes a record, it may not always be an accurate reflection of what happened. “You might have a video record of what I said and what the patient said, but the camera doesn’t tell the whole story,” said Wright. “There are nuances, and there may be family members who are not on camera…you have to consider that something may be missing.”

Most EDs have wall-mounted security cameras; a 2023 study found that 94.7% had security cameras in key locations. Signage alerting patients of cameras is also common; more than half of EDs have signage warning patients and visitors that they are being recorded, so there may be little expectation of privacy in public areas. But unfortunately, sometimes, patients must be triaged, and treated, in the hallways of busy EDs, where they are subject to being recorded either on stationary or body-worn cameras.

 

Keeping the ED Safe

Putting aside privacy concerns, security measures meant to protect staff and patients can only do so much. “Some security measures are more of a feel-good measure,” said Wright. “We have automatic door locks for our doors, but the whole side of the building is glass…my personal feeling is that cameras can be a deterrent, but if someone has an intention to hurt someone else or is psychotic, you aren’t going to be able to stop them from what they’re going to do.”

Regardless, we’re likely to see more security measures like body-worn cameras in the ED. “Workplace safety is very much on the minds of ER physicians and ER nurses,” said Goodloe. “EDs have become sites of workplace violence with unacceptable increasing frequency…how do we solve this, [while] simultaneously not discouraging or preventing access to emergency care when and where people need it most?”

“We truly care about patient safety and our colleagues’ safety, and we want to be able to come in and make a positive difference,” said Goodloe. But ultimately, doctors want to go home safely to their families, and they want their patients to be able to do that, too.

 

A version of this article appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them. 

The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials. 

During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities. 

In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.

Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.

But is that really the case? 

A recent survey published in The Lancet Oncology aimed to tease out people’s preferences for confirmed clinical benefit vs speedier access. The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works. 

In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios. 

The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).

The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).

The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios. 

Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty. 

Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.

“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.

Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview. 

In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.

“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.

Bishal Gyawali, MD, PhD, was not surprised by the findings. 

“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview. 

“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”

However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added. 

What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.

The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.

A version of this article first appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists led to a significant reduction in the risk for venous thromboembolism (VTE) among individuals with type 2 diabetes, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, a recent analysis indicated.

Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.

The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.

In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.

After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.

The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.

Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).

The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.

Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).

The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).

Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.

Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.

“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”

This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists led to a significant reduction in the risk for venous thromboembolism (VTE) among individuals with type 2 diabetes, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, a recent analysis indicated.

Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.

The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.

In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.

After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.

The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.

Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).

The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.

Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).

The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).

Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.

Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.

“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”

This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) receptor agonists led to a significant reduction in the risk for venous thromboembolism (VTE) among individuals with type 2 diabetes, compared with dipeptidyl peptidase 4 (DPP-4) inhibitors, a recent analysis indicated.

Overall, GLP-1 agonist use was associated with a 20% reduction in VTE, compared with DPP-4 inhibitor use, in those with type 2 diabetes, and this benefit held regardless of people’s obesity status, said study investigator Cho-Han Chiang, MD, a medical resident at Mount Auburn Hospital, Cambridge, Massachusetts, who presented the findings at the American Society of Hematology (ASH) 2024 Annual Meeting.

The incidence of VTE has increased by 20% over the past 10 years, and obesity is a risk factor for VTE, Chiang explained. A growing body of evidence demonstrated that GLP-1s provide a variety of cardiovascular benefits in people with type 2 diabetes, but data on VTE benefits remain more limited.

In the retrospective study, the researchers combed electronic health records from the TriNetX global database, which includes more than 250 million patients, and identified adults with type 2 diabetes who were taking a GLP-1 agonist or a DPP-4 inhibitor.

After excluding anyone with prior VTE or atrial fibrillation as well as those treated with both drugs or with oral anticoagulants, patients on GLP-1s were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, body mass index (BMI), hemoglobin A1c, use of other antidiabetic agents, and underlying comorbidities. VTE was a composite of pulmonary embolism and deep vein thrombosis.

The researchers also performed a subgroup analysis that stratified patients by obesity status, defined as a BMI ≥ 30.

Within 1 year of GLP-1 or DPP-4 prescription, VTE occurred at a rate of 6.5 cases/1000 person-years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (hazard ratio [HR], 0.80; P < .001).

The 20% risk reduction in VTE held across various subgroups of BMI, including among those with obesity, Chiang reported.

Among patients with the highest BMI (≥ 40), VTE occurred at a rate of 7.2 cases/1000 person years in the GLP-1 group vs 9.6 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.74). Among patients with the next highest BMI (30-34.9), VTE occurred at a rate of 4.8 cases/1000 person years in the GLP-1 group vs 7.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.60). Among those with the lowest BMI (18.5-24.9), VTE occurred significantly less frequently among those in the GLP-1 group — 4.7 cases/1000 person years vs 7.4 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.61).

The lower risk for VTE associated with GLP-1s also held across the individual components of the composite VTE. Pulmonary embolism occurred at a rate of 3.1 cases/1000 person years in the GLP-1 group vs 3.9 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.78), and deep vein thrombosis occurred in 4.2 cases/1000 person years in the GLP-1 group vs 5.0 cases/1000 person years in the DPP-4 inhibitor group (HR, 0.82).

Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date, said Chiang.

Session moderator Ghadeer Dawwas, PhD, said in an interview that patients with type 2 diabetes are increasingly using GLP-1 agonists because of the cardiovascular benefits associated with the agents, which include lower risks for stroke and heart failure, but the antithrombotic benefits are still debated.

“The current study indicates that GLP-1 agonists may help lower the risk of VTE in patients with type 2 diabetes, irrespective of their baseline body weight,” said Dawwas, a pharmacoepidemiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. “However, given the current landscape of evidence and the existence of conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”

This study was funded by the National Blood Clot Alliance and Conquer Cancer Foundation. Chiang and Dawwas had no disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

SAN DIEGO — Significant complications were common in female patients with sickle cell disease (SCD) who underwent fertility preservation (FP) procedures, and 13% required multiple retrieval cycles, a five-center retrospective study found.

Of 46 patients with SCD, complications occurred in 25 of 55 controlled ovarian hyperstimulation cycles, including 29 vaso-occlusive episodes (VOEs), researchers reported at the American Society of Hematology (ASH) 2024 Annual Meeting.

Of 21 post-retrieval VOEs, 19 required emergency department care or hospitalization.

“Baseline sickle cell disease severity is most likely associated with a patient’s risk of complications from an egg retrieval cycle,” study co-author Sarah Cromack, MD, a reproductive endocrinology and infertility fellow at Northwestern University, Chicago, said in an interview.

“Both hematologists and reproductive endocrinologists can use this information to plan ahead and anticipate possible issues, check blood counts prior to and after egg retrieval to see if transfusion is needed, and plan close follow-up during stimulation and immediately after egg retrieval to evaluate and treat pain.”

 

SCD Accelerates Decline in Ovarian Reserve

Pediatric hematologist Lydia H. Pecker, MD, MS, of Johns Hopkins University School of Medicine, Baltimore, the study’s corresponding author, said in an interview that SCD is “a disease of accelerated aging” that leads to accelerated decline in ovarian reserve. “The common indication for fertility preservation in SCD is before bone marrow transplant or gene therapy,” she said, although FP can also be offered to other patients with SCD.

According to Cromack, researchers launched the study to expand information about SCD and FP in light of sparse data about outcomes.

All the 46 patients had hemoglobin SS (HbSS, 93%) and HbSβ0-thalassemia (7%) and a median age of 23.7 (18-28) years. Almost all (44 patients) underwent FP prior to curative treatments, and all had at least one SCD-related complication, mainly cerebrovascular disease (16), acute chest syndrome (23), and more than two VOEs per year (31).

Median anti-Mullerian hormone (AMH) level (2.1 ng/mL), a measurement of ovarian reserve, was lower than the expected level of 2.8-3.4 ng/mL among women in the age range of the patients, the researchers reported. “This is consistent with previous studies showing lower AMH for age in women with sickle cell disease,” Pecker said.

 

Complications in 45% of Retrieval Cycles

“In terms of success of oocyte cryopreservation, the median number of mature eggs frozen was 11,” said co-author and reproductive endocrinologist Jessica Walter, MD, of Northwestern University, in an interview. “Given the average age of 24 years in the cohort, this would give each patient about a 70% estimated probability of at least one live birth from their cohort of frozen eggs. Thus, patients hoping for more than one child may want to consider more than one cycle of egg freezing.”

The rate of complications was “fairly high” at 45% of all cycles, Walter said. “These were mostly complications from underlying sickle cell disease, including unplanned transfusions and admissions for vaso-occlusive crises. Surprisingly, there were very few cases of ovarian hyperstimulation syndrome in this young patient group, which may be due to a combination of underlying vascular disease, lower peak estradiol levels, and slightly less eggs retrieved then would be expected compared to an age-matched healthy controls.”

Any FP complication was associated with more than three VOEs in the year before controlled ovarian hyperstimulation (mean of three VOEs per patient without complications vs six per patient with complications; P = .036).

 

Higher Than Normal Need for Multiple Cycles

Reproductive endocrinologist H. Irene Su, MD, professor and co-director of the Center for OB/GYN Research Innovations at Moores Cancer Center, University of California San Diego, praised the study as “an important report” in an interview.

Su, who wasn’t involved in the research, said the percentage of patients requiring more than one cycle due to cancellation or low oocyte yield — 13% — is “higher than expected, given the young age of this cohort.”

This could reflect the hypothesis that “sickle cell crises and hypoxia adversely affect the finite number of oocytes in the ovary,” she said.

As for the study findings regarding complications, she said the rate “is very high compared to the general infertility or fertility preservation population. It would be good to learn predictors of these outcomes so that fertility and hematology clinicians can work together to stratify risk and supportive services around FP cycles. It would also be good to know if the post-retrieval VOE were unexpected given the patient’s disease activity prior to FP.”

 

Message: FP in SCD Is Feasible, Acceptable

A.D. Mishkin, MD, MPH, associate professor of psychiatry and liaison to the Blood and Marrow Transplantation Program at NewYork–Presbyterian/Columbia University Irving Medical Center, New York City, said in an interview that the study “establishes the feasibility and acceptability of oocyte harvest and preservation in a population of patients with active ongoing symptoms from SCD. It also indicates their interest in pursuing fertility preservation in the setting of frequent crises and the potential for management of ensuing complications.”

Mishkin, who didn’t take part in the research, highlighted the finding that half the patients got access to FP via public insurance or research funding. “Even in this population where most women had multiple complications in the year prior to FP, and even among patients who needed multiple retrievals, these patients wanted to go through that risk to preserve their fertility,” Mishkin said. “This is an important finding given the very limited access many individuals have to FP due to its high cost and limited insurance coverage, which is also largely state-dependent.”

There’s another factor to consider regarding SCD and FP: The potential danger of pregnancy.

Corresponding author Pecker noted that “pregnancy is high risk for people with sickle cell disease. There are very high rates of severe maternal mortality and morbidity even in high-income countries. However, some of this is modifiable with routine use of chronic transfusions during pregnancy and with high-quality and integrated expert SCD and expert maternal fetal medicine care during pregnancy.”

The National Institutes of Health supported the research. Pecker reported receiving research funding from Alexion, Novartis, and Aummune and consulting for Novo Nordisk. Other authors reported no disclosures. Su and Mishkin reported no disclosures.

 

A version of this article appeared on Medscape.com.

We have a tradition at Federal Practitioner where the December editorial usually features some version of the “best and worst” of the last 12 months in government health care. As we close out a difficult year, instead I offer a cautionary yet promising story that epitomizes both risk and benefit.

In some quarters, 2024 has been the year of AI (artificial intelligence).² While in science fiction, superhuman machines, like the Terminator, are often associated with apocalyptic threats, we often forget the positive models of human-technology interaction, such as the protective robot in Lost in Space. While AI is not yet as advanced as what has already been depicted on the screen, it is inextricably interwoven into the daily fabric of our lives. Almost any website you go to for business or pleasure has a chatbot waiting to help (or frustrate) you. Most of us have Alexa, Siri, or another digital assistant organizing our homes and schedules. When I Google “everyday uses of artificial intelligence,” it is AI that responds with an overview.

Medicine is not immune. Renowned physician and scientist Eric Topol, MD, suggests that AI represents a “fourth industrial revolution in medicine” that can dramatically improve health care.³ The US Department of Veterans Affairs (VA) has been at the forefront of this new space.⁴ The story recounted below encapsulates the enormous benefits AI can bring to health care and the vigilance we must exercise to anticipate and mitigate risk for this to be an overall positive transition.

The story begins with a key element of AI change—the machine learning predictive algorithm. In this case, the algorithm was designed to predict—and thereby prevent—the top public health priority in federal practice: suicide. The Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET) program was launched in 2017 to assist in identifying the top 0.1% of veterans at the highest risk for suicide.⁵

At least at this stage of AI in medicine, the safest and most ethical efforts come from collaborations between health care professionals and AI developers that maximize the very different strengths of each partner. REACH VET is an exemplar of this kind of teamwork. Once the algorithm analyzes > 60 variables to identify veterans at high risk for suicide, data are communicated to a REACH VET program coordinator, who then notifies the practitioner responsible for the veteran’s care so they can put into action evidence-based suicide prevention strategies.⁵

VA researchers in 2021 published a study of 173,313 veterans comparing outcomes before and after entry into the program using a triple differences design. Veterans participating in the program reported an increase in outpatient visits and documentation of safety plans, and a decrease in emergency department visits, inpatient mental health admissions, and recorded suicide attempts.⁶

A US Government Accounting Office analysis found that “REACH VET had identified veterans who had not been identified through other methods.”⁷ This was not just an example of AI hype: as a relatively rare and statistically complicated phenomenon, suicide is notoriously difficult to predict and model. Machine learning algorithms like REACH VET have unprecedented potential to assist and augment suicide prevention.⁸

In 2023, veteran service organizations and journalists raised concerns that the AI algorithm was biased and ignored critical risk factors that put some veterans at increased risk. Based on their analysis, they claimed that the algorithm did not account for risk factors uniquely associated with women veterans, namely military sexual trauma and intimate partner violence.⁹ Women are the most rapidly growing VA population, yet too often they encounter health care disparities, harassment, and stigmatization when seeking care. The Congressional Veterans Affairs committees investigated and introduced legislation to update the algorithm.¹⁰

VA experts dispute these claims, and a computer science PhD may be required to understand the debate. But as the history of medicine has shown us, every treatment and procedure has benefits and risks. No matter how bright and shiny the technology initially appears, a soft scientific underbelly emerges sooner or later. Just as with REACH VET, algorithm bias is often discovered during deployment when the logic of the laboratory encounters the unpredictable variety of humankind.¹¹ Frequently, those problems are—as with REACH VET— not solely or even primarily technical ones. The data mirror society and reflect its biases.

For learning organizations like the VA and the US Department of Defense (DoD), the criticisms of REACH VET signal the need to engage in continuous performance improvement. AI requires the human trainers and supervisors who teach the machines to continuously revise and update their lesson plans. The most recent VA data show that in 2021, 6392 veterans died by suicide.¹² In Congressional testimony, VA leaders reported that as of May 2024, REACH VET was operating in 28 VA facilities and had identified 6700 high-risk veterans.13 REACH VET can save veteran’s lives, which is the sine qua non for our federal health care systems.

The algorithm should be improved to identify ALL veterans so they receive lifesaving interventions. Every veteran’s life is sacred; the algorithm that may prevent suicide must be continuously improved. That is why our representatives did not propose to ban REACH VET or enforce an AI winter on the VA and DoD. Instead, they called for an update to the algorithm, underscoring the value of machine learning for suicide prediction and prevention.

The epigraph from one of the top AI ethicists and scientists in the world makes the point that AI is not the moral agent here: it is fallible humans who must keep learning along with machines. That is why, at the end of 2024, VA experts are revising the algorithm so REACH VET can help prevent even more veteran suicides in 2025 and beyond.¹⁴

We have a tradition at Federal Practitioner where the December editorial usually features some version of the “best and worst” of the last 12 months in government health care. As we close out a difficult year, instead I offer a cautionary yet promising story that epitomizes both risk and benefit.

In some quarters, 2024 has been the year of AI (artificial intelligence).² While in science fiction, superhuman machines, like the Terminator, are often associated with apocalyptic threats, we often forget the positive models of human-technology interaction, such as the protective robot in Lost in Space. While AI is not yet as advanced as what has already been depicted on the screen, it is inextricably interwoven into the daily fabric of our lives. Almost any website you go to for business or pleasure has a chatbot waiting to help (or frustrate) you. Most of us have Alexa, Siri, or another digital assistant organizing our homes and schedules. When I Google “everyday uses of artificial intelligence,” it is AI that responds with an overview.

Medicine is not immune. Renowned physician and scientist Eric Topol, MD, suggests that AI represents a “fourth industrial revolution in medicine” that can dramatically improve health care.³ The US Department of Veterans Affairs (VA) has been at the forefront of this new space.⁴ The story recounted below encapsulates the enormous benefits AI can bring to health care and the vigilance we must exercise to anticipate and mitigate risk for this to be an overall positive transition.

The story begins with a key element of AI change—the machine learning predictive algorithm. In this case, the algorithm was designed to predict—and thereby prevent—the top public health priority in federal practice: suicide. The Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET) program was launched in 2017 to assist in identifying the top 0.1% of veterans at the highest risk for suicide.⁵

At least at this stage of AI in medicine, the safest and most ethical efforts come from collaborations between health care professionals and AI developers that maximize the very different strengths of each partner. REACH VET is an exemplar of this kind of teamwork. Once the algorithm analyzes > 60 variables to identify veterans at high risk for suicide, data are communicated to a REACH VET program coordinator, who then notifies the practitioner responsible for the veteran’s care so they can put into action evidence-based suicide prevention strategies.⁵

VA researchers in 2021 published a study of 173,313 veterans comparing outcomes before and after entry into the program using a triple differences design. Veterans participating in the program reported an increase in outpatient visits and documentation of safety plans, and a decrease in emergency department visits, inpatient mental health admissions, and recorded suicide attempts.⁶

A US Government Accounting Office analysis found that “REACH VET had identified veterans who had not been identified through other methods.”⁷ This was not just an example of AI hype: as a relatively rare and statistically complicated phenomenon, suicide is notoriously difficult to predict and model. Machine learning algorithms like REACH VET have unprecedented potential to assist and augment suicide prevention.⁸

In 2023, veteran service organizations and journalists raised concerns that the AI algorithm was biased and ignored critical risk factors that put some veterans at increased risk. Based on their analysis, they claimed that the algorithm did not account for risk factors uniquely associated with women veterans, namely military sexual trauma and intimate partner violence.⁹ Women are the most rapidly growing VA population, yet too often they encounter health care disparities, harassment, and stigmatization when seeking care. The Congressional Veterans Affairs committees investigated and introduced legislation to update the algorithm.¹⁰

VA experts dispute these claims, and a computer science PhD may be required to understand the debate. But as the history of medicine has shown us, every treatment and procedure has benefits and risks. No matter how bright and shiny the technology initially appears, a soft scientific underbelly emerges sooner or later. Just as with REACH VET, algorithm bias is often discovered during deployment when the logic of the laboratory encounters the unpredictable variety of humankind.¹¹ Frequently, those problems are—as with REACH VET— not solely or even primarily technical ones. The data mirror society and reflect its biases.

For learning organizations like the VA and the US Department of Defense (DoD), the criticisms of REACH VET signal the need to engage in continuous performance improvement. AI requires the human trainers and supervisors who teach the machines to continuously revise and update their lesson plans. The most recent VA data show that in 2021, 6392 veterans died by suicide.¹² In Congressional testimony, VA leaders reported that as of May 2024, REACH VET was operating in 28 VA facilities and had identified 6700 high-risk veterans.13 REACH VET can save veteran’s lives, which is the sine qua non for our federal health care systems.

The algorithm should be improved to identify ALL veterans so they receive lifesaving interventions. Every veteran’s life is sacred; the algorithm that may prevent suicide must be continuously improved. That is why our representatives did not propose to ban REACH VET or enforce an AI winter on the VA and DoD. Instead, they called for an update to the algorithm, underscoring the value of machine learning for suicide prediction and prevention.

The epigraph from one of the top AI ethicists and scientists in the world makes the point that AI is not the moral agent here: it is fallible humans who must keep learning along with machines. That is why, at the end of 2024, VA experts are revising the algorithm so REACH VET can help prevent even more veteran suicides in 2025 and beyond.¹⁴

We have a tradition at Federal Practitioner where the December editorial usually features some version of the “best and worst” of the last 12 months in government health care. As we close out a difficult year, instead I offer a cautionary yet promising story that epitomizes both risk and benefit.

In some quarters, 2024 has been the year of AI (artificial intelligence).² While in science fiction, superhuman machines, like the Terminator, are often associated with apocalyptic threats, we often forget the positive models of human-technology interaction, such as the protective robot in Lost in Space. While AI is not yet as advanced as what has already been depicted on the screen, it is inextricably interwoven into the daily fabric of our lives. Almost any website you go to for business or pleasure has a chatbot waiting to help (or frustrate) you. Most of us have Alexa, Siri, or another digital assistant organizing our homes and schedules. When I Google “everyday uses of artificial intelligence,” it is AI that responds with an overview.

Medicine is not immune. Renowned physician and scientist Eric Topol, MD, suggests that AI represents a “fourth industrial revolution in medicine” that can dramatically improve health care.³ The US Department of Veterans Affairs (VA) has been at the forefront of this new space.⁴ The story recounted below encapsulates the enormous benefits AI can bring to health care and the vigilance we must exercise to anticipate and mitigate risk for this to be an overall positive transition.

The story begins with a key element of AI change—the machine learning predictive algorithm. In this case, the algorithm was designed to predict—and thereby prevent—the top public health priority in federal practice: suicide. The Recovery Engagement and Coordination for Health-Veterans Enhanced Treatment (REACH VET) program was launched in 2017 to assist in identifying the top 0.1% of veterans at the highest risk for suicide.⁵

At least at this stage of AI in medicine, the safest and most ethical efforts come from collaborations between health care professionals and AI developers that maximize the very different strengths of each partner. REACH VET is an exemplar of this kind of teamwork. Once the algorithm analyzes > 60 variables to identify veterans at high risk for suicide, data are communicated to a REACH VET program coordinator, who then notifies the practitioner responsible for the veteran’s care so they can put into action evidence-based suicide prevention strategies.⁵

VA researchers in 2021 published a study of 173,313 veterans comparing outcomes before and after entry into the program using a triple differences design. Veterans participating in the program reported an increase in outpatient visits and documentation of safety plans, and a decrease in emergency department visits, inpatient mental health admissions, and recorded suicide attempts.⁶

A US Government Accounting Office analysis found that “REACH VET had identified veterans who had not been identified through other methods.”⁷ This was not just an example of AI hype: as a relatively rare and statistically complicated phenomenon, suicide is notoriously difficult to predict and model. Machine learning algorithms like REACH VET have unprecedented potential to assist and augment suicide prevention.⁸

In 2023, veteran service organizations and journalists raised concerns that the AI algorithm was biased and ignored critical risk factors that put some veterans at increased risk. Based on their analysis, they claimed that the algorithm did not account for risk factors uniquely associated with women veterans, namely military sexual trauma and intimate partner violence.⁹ Women are the most rapidly growing VA population, yet too often they encounter health care disparities, harassment, and stigmatization when seeking care. The Congressional Veterans Affairs committees investigated and introduced legislation to update the algorithm.¹⁰

VA experts dispute these claims, and a computer science PhD may be required to understand the debate. But as the history of medicine has shown us, every treatment and procedure has benefits and risks. No matter how bright and shiny the technology initially appears, a soft scientific underbelly emerges sooner or later. Just as with REACH VET, algorithm bias is often discovered during deployment when the logic of the laboratory encounters the unpredictable variety of humankind.¹¹ Frequently, those problems are—as with REACH VET— not solely or even primarily technical ones. The data mirror society and reflect its biases.

For learning organizations like the VA and the US Department of Defense (DoD), the criticisms of REACH VET signal the need to engage in continuous performance improvement. AI requires the human trainers and supervisors who teach the machines to continuously revise and update their lesson plans. The most recent VA data show that in 2021, 6392 veterans died by suicide.¹² In Congressional testimony, VA leaders reported that as of May 2024, REACH VET was operating in 28 VA facilities and had identified 6700 high-risk veterans.13 REACH VET can save veteran’s lives, which is the sine qua non for our federal health care systems.

The algorithm should be improved to identify ALL veterans so they receive lifesaving interventions. Every veteran’s life is sacred; the algorithm that may prevent suicide must be continuously improved. That is why our representatives did not propose to ban REACH VET or enforce an AI winter on the VA and DoD. Instead, they called for an update to the algorithm, underscoring the value of machine learning for suicide prediction and prevention.

The epigraph from one of the top AI ethicists and scientists in the world makes the point that AI is not the moral agent here: it is fallible humans who must keep learning along with machines. That is why, at the end of 2024, VA experts are revising the algorithm so REACH VET can help prevent even more veteran suicides in 2025 and beyond.¹⁴

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

Recipients of allogeneic hematopoietic cell transplantation (allo-HCT) for blood disorders who maintain diets high in fiber show significant improvements in overall survival and a reduced risk of developing the potentially life-threatening complication of acute graft-versus-host disease (aGVHD), new research shows.

Importantly, the findings suggest standard recommendations for patients of a low-fiber diet following allo-HCT may run counter to the potential benefits. 

“Significant decrease of fiber intake during transplantation is detrimental. It’s a lost opportunity to promote a healthy gut microbiome, recover from treatment-related microbiota injury, and protect against GVHD,” first author Jenny Paredes, PhD, a staff scientist at City of Hope National Medical Center in Duarte, California, said in a press statement for the study presented at the American Society of Hematology (ASH) 2024 Annual Meeting.

Although the health benefits of dietary fiber on the gut microbiome are well-documented, the effects have recently been shown to extend to outcomes after allo-HCT in general, with researchers finding increased overall survival when there is higher diversity in the gut microbiome, including a higher abundance of butyrate producers and lower abundance of enterococcus, explained Paredes when presenting the findings.

Acute GvHD, a common and potentially life-threatening complication of allo-HCT, can have symptoms that mimic irritable bowel disease (IBD), including abdominal pain or cramps, nausea, vomiting, and diarrhea. The low-fiber diet recommendations, including avoidance of raw vegetables and fruits before and after the allo-HCT procedure, are designed to counter those effects, as well as reduce exposure to bacteria.

However, with data suggesting the potential benefits of dietary fiber could extend to the prevention of GvHD, Paredes and colleagues further investigated.

For the observational study, they evaluated all dietary data on 173 allo-HCT recipients at Memorial Sloan Kettering Cancer Center (MSKCC) from 10 days prior to transplantation to 30 days post-transplantation, representing 3837 patient-days in total.

Data collected from the patients also included rRNA sequencing of fecal samples and fecal short-chain fatty acid concentration. 

Participants had a median age of 60, and 45% were female. The most common diseases being treated were leukemia (50%), myelodysplastic syndrome (25%), and non-Hodgkin’s lymphoma (8.7%).

After stratifying patients based on high- or low-fiber intake, those with high-fiber intake were found to have significantly higher rates of microbial α-diversity (P = .009), a higher abundance of butyrate producers (P = .03), and a higher concentration of butyrate (P = .02), a short-chain fatty acid that plays a key role in gut health. 

Furthermore, the high-fiber group had significantly higher overall survival in an analysis extending to 24 months relative to day 12 of the study (P = .04).

Focusing on GvHD outcomes, the authors further evaluated data on 101 non-T-cell–depleted patients, and identified 29 patients without GvHD and 24 who developed lower gastrointestinal (GI) GvHD. 

Patients with lower GI GvHD had significantly lower fecal concentrations of butyrate (P = .03) and acetate (P = .02).

However, patients among those in the high-fiber intake group had a significantly lower cumulative incidence of developing GvHD at day 100 (P = .034) and a lower incidence of lower GI GvHD (P = .04).

A separate preclinical analysis of a mouse model with GvHD further showed that a fiber-rich diet (12% cellulose) significantly increased the expression of genes associated with reduced GvHD, including IDO1 and CEACAM1, and those associated with enrichment of the bile acid pathway.

The findings suggest an opportunity to improve outcomes with relatively small dietary changes, Paredes said.

“Strategies to increase the fiber concentration in these diets paired with the safety that these patients need is what makes this study exciting,” she said in an interview. 

“Increasing the fiber intake by 10 to 20 grams/day could potentially increase the microbiome diversity and abundance of butyrate producers, which have been correlated with higher overall survival rates post allo-HCT,” she continued.

“[For instance], that could be an avocado per day, or it could be a small salad per day, or a small vegetable soup per day,” she added. “I would encourage institutions to re-evaluate their menu planning and see how to include more fiber into the meals in a safe way.”

Ultimately, “I think that a dietary intervention outweighs the risks of a pharmacological intervention,” Paredes added.

The necessary duration of a high-fiber diet to produce the beneficial effects on allo-HCT outcomes would likely be over the course of the pre- and post-transplant periods, Paredes added.

“With the survival analysis extending from 5 days before transplantation to 12 days post, we are looking at an intervention that potentially could be around 20 days,” she said.

“We would love to take advantage of the pretransplantation window, in particular, and we can see that just increasing the fiber intake by about 20 grams during this window was shown to improve overall survival after 24 months,” Paredes added.

Importantly, however, some patients may not be appropriate for high-fiber dietary changes, Paredes cautioned. 

“Patients that have developed IBD-like symptoms and severe GvHD patients, for example, or with lower GI-GvHD grades 3 and 4 would be not appropriate candidates for a high-fiber diet,” she said. 

 

High-Fiber Diet Slows MM Disease Progression?

The potential important benefits of a high-fiber diet in blood diseases were further demonstrated in a separate study also by MSKCC researchers presented at the meeting, which showed encouraging signs that a plant-based diet rich in fiber could potentially slow disease progression in multiple myeloma (MM).

NUTRIVENTION included 20 patients with the two precancerous MM conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which can last for years without progressing to MM and which researchers have speculated could be a potential opportunity to intervene to prevent progression to cancer.

Patients were provided with a 12-week controlled diet plus health coaching for another 3 months; no meals or coaching were provided for the rest of the 1-year study period. Participants had a median age of 62 and, with being overweight/obesity a risk factor for MM, had a body mass index (BMI) of 25 kg/m² or higher.

The trial met its endpoint of feasibility, with 91% adherence in the first 3 months. The rate of consumption of unprocessed plant foods increased from 20% at baseline to 92% on the intervention. Overall adherence was 58%. Insulin and anti-inflammatory markers also improved and, despite no calorie restriction, there was a 7% sustained reduction in BMI. 

Notably, two patients in the study had stabilization of disease progression.

“We saw improvements in all spheres, including metabolism, microbiome, and immune system markers, and we also saw that two patients with progressive disease had the progression stabilize and slow down on the intervention,” principal investigator Urvi A. Shah, MD, said in a press statement. 

“Even though it’s just two cases, to our knowledge, it has not been shown before in an intervention setting that you can improve diet and lifestyle and actually slow or change the trajectory of the disease,” she noted.

The researchers caution that findings in mice do not necessarily translate to humans but note another experiment in mice with SMM that showed animals fed a normal diet had progression to MM after a median of 12 weeks, compared with a median of 30 weeks among those fed a high-fiber diet.

Notably, all mice in the normal-diet group progressed to MM, whereas 40% of mice in the high-fiber group did not. 

“We found that a high-fiber plant-based diet can improve BMI, improve insulin resistance [and] the microbiome through diversity and butyrate producers, and with the production of short-chain fatty acids, can have effects on inflammation, immunity, innate and adaptive antitumor immunity, and tumor cells or plasma cells,” Shah said during her presentation.

The study was supported by funding from the National Cancer Institute and private foundations. Paredes has reported no relevant financial relationships. Shah has reported relationships with Sanofi, Bristol Myers Squibb, and Janssen.

A version of this article first appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lipid-lowering drugs, were associated with a 22% lower risk for nonmelanoma skin cancer (NMSC) in patients with atherosclerotic cardiovascular disease (ASCVD), an effect that was particularly significant among men, those older than 65 years, and those with immunosuppression.

METHODOLOGY:

• To evaluate the risk for NMSC — basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) — in patients with ASCVD on PCSK9 inhibitors, researchers analyzed data from the US Collaborative Network in the TriNetX database of adults aged ≥ 40 years with ASCVD who received statin therapy between 2016 and 2022.
• A total of 73,636 patients were included, divided equally between those receiving a PCSK9 inhibitor (evolocumab, alirocumab, or inclisiran) plus statin therapy and the control group (those on statin therapy only).
• The analysis used propensity score matching for head-to-head comparisons, with hazard ratios (HRs) estimated using Cox proportional hazard models.
• Stratified analyses examined outcomes by age, sex, Fitzpatrick skin type, and immune status. (Immunosuppressed patients were those treated with immunosuppressants for more than 90 days in the year before the index date — the date when exposed patients were first prescribed a PCSK9 inhibitor, which was also index date for matched patients in the statin-only group.)

TAKEAWAY:

• Patients with ASCVD in the PCSK9 group showed significantly lower risks for NMSC (HR, 0.78; 95% CI, 0.71-0.87), BCC (HR, 0.78; 95% CI, 0.69-0.89), and SCC (HR, 0.79; 95% CI, 0.67-0.93) than control individuals on a statin only (P < .001 for all three).
• Both evolocumab and alirocumab demonstrated similar protective effects against the development of NMSC.
• The reduced risk for NMSC was particularly notable among patients aged 65-79 years (HR, 0.75; 95% CI, 0.66-0.86) and those aged ≥ 80 years (HR, 0.74; 95% CI, 0.60-0.91).
• Men showed a more pronounced reduction in the risk for NMSC (HR, 0.73; 95% CI, 0.64-0.83) than women (HR, 0.93; 95% CI, 0.78-1.11). The effect on lowering NMSC risk was also evident among immunosuppressed patients in the PCSK9 group (HR, 0.68; 95% CI, 0.60-0.75).

IN PRACTICE:

“The findings suggest the promising pleiotropic effect of PCSK9 inhibitors on the chemoprevention of NMSC,” the study authors wrote. Referring to previous studies that “provided mechanistic clues to our findings,” they added that “further studies are required to investigate the underlying mechanisms and establish causality.”

SOURCE:

The study was led by Cheng-Yuan Li, Taipei Veterans General Hospital, Taipei, Taiwan, and was published online in The British Journal of Dermatology.

LIMITATIONS:

Electronic health records lack information on sun protection habits, family history of skin cancer, diet, body mass index, and air pollution exposure, risk factors for NMSC. The study also lacked detailed information on enrollees’ lipid profiles and was focused mostly on patients in the United States, limiting the generalizability of the findings to other regions.

DISCLOSURES:

The study was supported by grants from Taipei Veterans General Hospital and the Ministry of Science and Technology, Taiwan. The authors reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

A version of this article first appeared on Medscape.com.

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

A version of this article first appeared on Medscape.com.

Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.

But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.

Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.

In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.

“A focus on neoantigens that arise from driver mutations in different tumor types could allow us to make progress in creating off-the-shelf vaccines,” said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.

“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.

Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.

“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”

Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.

 

Then: Where We Were

Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.

In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.

Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”

In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”

Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.

In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.

In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.

That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.

In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.

And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.

But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.

When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.

But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.

Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.

“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”

 

A Turning Point?

Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.

Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.

Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.

Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.

Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.

“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.” 

Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.

One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.

But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”

“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”

Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.

“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”

Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.

As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”

A version of this article first appeared on Medscape.com.