Conference Coverage

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.

Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.

“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.

BackyardProduction/Thinkstock

In addition to looking at the prevalence of inadequate pain relief ­– defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.

It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).

“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.

Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.

“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.

In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.

“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.

High rates of prescription opioid use before TKA

In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).

Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.

Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.

He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.

“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.

“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.

“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.

“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.

Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
 

Sharp rise in opioid use 2 years before TKA

Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.

The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.

The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.

“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.

“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.

In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.

The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.

The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.

Clinicians are struggling to make sense of conflicting regulations from the Food and Drug Administration and the European Medicines Agency on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.

“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.

He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.

Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.

Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.

PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.

Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.

In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.

Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
 

Pivotal decision-making clinical trials

The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.

KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.

In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.

The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.

Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.

Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.

“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.

Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.

“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.

JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.

ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.

Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.

The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”

In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.

Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.

Clinicians are struggling to make sense of conflicting regulations from the Food and Drug Administration and the European Medicines Agency on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.

“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.

He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.

Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.

Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.

PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.

Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.

In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.

Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
 

Pivotal decision-making clinical trials

The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.

KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.

In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.

The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.

Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.

Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.

“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.

Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.

“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.

JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.

ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.

Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.

The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”

In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.

Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.

Clinicians are struggling to make sense of conflicting regulations from the Food and Drug Administration and the European Medicines Agency on whether measuring programmed death–ligand 1 (PD-L1) is essential before prescribing checkpoint inhibitors for gastroesophageal cancer.

“In the last couple of years, the incorporation of PD-1 antibodies is really changing our standard of care and international guidelines in this disease,” said Ian Chau, MD, a consultant medical oncologist at the Royal Marsden Hospital, London.

He moderated a debate at the 2022 Gastrointestinal Cancers Symposium on the importance of measuring PD-L1 expression levels before administering immune checkpoint inhibitor therapy.

Tumor cells can use PD-1 signaling to deactivate the response of T cells that would otherwise destroy them, and several new drugs are designed to block that signaling.

Multiple randomized controlled trials have shown the benefit of adding such checkpoint inhibitors to chemotherapy for gastroesophageal cancer and currently, chemotherapy plus a checkpoint inhibitor is standard care, Dr. Chau said.

PD-1–blocking antibodies include pembrolizumab (Keytruda, Merck) for colorectal cancer, gastric cancer, esophageal cancer, hepatocellular carcinoma, and renal cell carcinoma, among other cancers. And, nivolumab (Opdivo, Bristol-Myers Squibb) approved for renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and esophageal squamous cell carcinoma, among other cancers.

Regulators differ on whether these treatments should be limited to patients whose expression level of PD-L1 reaches a defined threshold. The FDA has not required the measurement of any biomarker before starting therapy with either of these drugs. However, the EMA requires a PD-L1 combined positive score (CPS) of at least 10 for pembrolizumab and at least 5 for nivolumab.

In a poll conducted before the start of the debate, 83% of physician attendees said they favor of the EMA position, while 17% disagreed.

Florian Lordick, MD, PhD, director of the University of Leipzig (Germany) Cancer Center, argued that tests for PD-L1 expression are accurate. About half of patients have CPS of at least 1. And, pathologists are in agreement in interpreting the tests about 97% of the time.
 

Pivotal decision-making clinical trials

The EMA requires a PD-L1 assay primarily based on its interpretation of the data from KEYNOTE-590 and CheckMate-648.

KEYNOTE-590 included 749 patients with esophageal carcinoma who were randomized to receive either pembrolizumab with standard of care chemotherapy, or placebo and standard of care chemotherapy. Patients receiving pembrolizumab who had PD-L1 CPS scores of 10 or more survived a few months longer on average. But in a post hoc analysis, the investigators found that, in patients with PD-L1 CPS scores less than 10, the difference between the treatment and placebo groups was not statistically significant.

In CheckMate-648, 970 patients with esophageal carcinoma were randomized to receive nivolumab with ipilimumab, nivolumab with chemotherapy, or chemotherapy alone. Investigators used a slightly different measurement of PD-L1 tumor proportion score (TPS), in comparing chemotherapy plus nivolumab to chemotherapy alone for advanced esophageal squamous cell carcinoma.

The median survival time of patients with TPS of at least 1% was 15.4 months in the nivolumab group and 9.2 months in the control group. But among patients with a TPS of less than 1%, the median overall survival was 12.0 months in the nivolumab group and 12.2 in the control group. CPS thresholds of 5 or 1 resulted in similar effects.

Dr. Lordick cited a systematic review of four studies in press at ESMO Open. Hazard ratios for three of the studies favored immunotherapy only in patients with CPS of at least 10.

Deciding which patients to treat matters because these drugs are expensive, he said. A single dose of 240 mg nivolumab costs $7,228.70, and treatment for 1 year can cost $173,488.80 in addition to costs for hospitalization because of immune-related adverse events, labs, imaging, colonoscopy, and other related costs.

“This is a lot of money, isn’t it? It’s the same price the hospital pay for two registered nurses in the U.S., at least when we are talking about the average price. I’m not sure I want to spend this money for a drug that does not work,” Dr. Lordick said.

Aaron Scott, MD, an oncologist with the University of Arizona Cancer Center, Tucson, said that “patients and clinicians want and need options” because there may be other factors that should be considered.

“PD-L1 has shown inconsistent results. And while I agree it is the best that we have for predictive biomarker in the space, it is far from perfect. PD-L1 has not been predictive for response in a variety of settings and trials. In first-line, second-line, third-line trials we have examples where it does not predict response,” he said.

JUPITER06 compared toripalimab or placebo with paclitaxel and cisplatin for patients with esophageal squamous cell carcinoma. Patients who received toripalimab lived longer than patients who received the placebo, but within the toripalimab group, there was no difference in median overall survival between those patients above and those below the threshold of CPS 1.

ORIENT-15 compared sintilimab or placebo with chemotherapy as first-line therapy for patients with esophageal squamous cell carcinoma. Although the treatment group fared better, survival rates were the same whether patients were above or below the CPS 10 threshold.

Dr. Scott cited three other trials in which PD-L1 was not predictive of response to checkpoint inhibitors.

The differences among studies could be attributed to different assays, he said. “Where you biopsy and when you biopsy seems to matter.”

In a second opinion poll conducted after the presentations, the proportion of physician attendees saying PD-L1 was essential before initiating checkpoint inhibitors, dropped to about two-thirds.

Dr. Chau reported financial relationships with Bristol-Myers Squibb, Merck Serono, and other pharmaceutical companies. Dr. Lordick reported financial relationships Bristol-Myers Squibb, Merck Sharp & Dohme, Merck, and other pharmaceutical companies.

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

MANCHESTER, ENGLAND – A new treatment option may soon be available for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

Zanubrutinib (Brukinsa), an irreversible, next-generation Bruton tyrosine kinase (BTK) inhibitor, is designed to minimize the off-target cardiovascular toxicities, such as atrial fibrillation and hypertension, seen with the first-generation ibrutinib (Imbruvica).

Zanubrutinib is already approved for use in mantle cell and marginal zone lymphomas and Waldenström’s macroglobulinemia.

Now it has also shown efficacy in CLL. In two phase 3 clinical trials, zanubrutinib has shown improved outcomes and reduced toxicity when compared with more established treatments in patients with relapsed/refractory and untreated CLL and SLL.

However, experts question whether the drug will find its place in an increasingly crowded space for the management of CLL.
 

Data from two phase 3 trials

The new data from two phase 3 clinical trials were presented recently at the British Society for Haematology 62nd annual scientific meeting, held in Manchester, England.

The ALPINE trial compared zanubrutinib with ibrutinib in 415 patients with CLL/SLL and showed that the novel drug was associated with a significant improvement in overall response rate, at 78% versus 63%.

This first interim analysis also showed that there was an increase in progression-free survival (PFS) with zanubrutinib, and crucially, it was associated with a lower atrial fibrillation/flutter rate than ibrutinib.

“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes,” said lead author Peter Hillmen, MBChB, FRCP, PhD, St. James’s University Hospital, Leeds, England.

The SEQUOIA study looked at zanubrutinib versus bendamustine plus rituximab in patients with untreated CLL/SLL with a 17p deletion and showed that PFS was improved with zanubrutinib by 58%.

Zanubrutinib was also associated with improved overall response rates and was well tolerated.

The results therefore “support the potential utility of zanubrutinib in the frontline management of patients with previously untreated CLL/SLL,” said lead author Talha Munir, MBBS, also of St. James’s University Hospital.
 

Improvement over ibrutinib

Ibrutinib, the first BTK inhibitor, “truly revolutionized the way we treat CLL,” commented Renata Walewska, MRCP, PhD, consultant hematologist at the Royal Bournemouth (England) Hospital and chair of the UKCLL Forum.

“But it has got quite a lot of, especially cardiac, problems, with atrial fibrillation and hypertension,” she said in an interview. The problem is that it acts not only as an inhibitor of Bruton kinase, but also affects other kinases, she explained.

Zanubrutinib is “much cleaner,” continued Dr. Walewska, who was lead author of the recently published British Society of Haematology guideline for the treatment of CLL.

However, the drug “is not that groundbreaking,” she commented, as acalabrutinib (Calquence), another next-generation BTK inhibitor, is already available for use in the clinic.

“We’re really lucky in CLL,” Dr. Walewska said, “we’ve got so many new drugs available, and it’s getting quite crowded. Trying to find a place for zanubrutinib is going be tricky.”

Lee Greenberger, PhD, chief scientific officer at the Leukemia & Lymphoma Society, commented that he “gives a lot of credit” to BeiGene, the company behind zanubrutinib, for “taking on these big studies.”

He said that, with the improvements in PFS and reduced atrial fibrillation with the drug, “there will be many clinicians paying attention to this and zanubrutinib could be preferred over conventional options.”

However, he agreed that it will have to compete with acalabrutinib, adding that, beyond BTK inhibitors, there are “a lot of options” for patients with CLL.

“That makes it very difficult for physicians to figure out what is the best type of therapy” to use in these patients, he added.

Dr. Greenberger told this news organization that further studies will need to demonstrate that zanubrutinib is associated with extended survival, which is “just not possible to show” at the moment with the current follow-up period.

He also noted that, in 10 years, ibrutinib will be off-patent, but zanubrutinib will not, at which point the “substantial” cost of the medication, which is a source of “hardship to patients,” will be increasingly relevant.
 

Study details

The phase 3 ALPINE study involved 415 adults with CLL/SLL refractory to one or more prior systemic therapies and measurable lymphadenopathy on imaging.  

They were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or withdrawal from the study.

Most patients had Binet stage A/B or Ann Arbor stage I/II disease, and 7.3% of patients treated with zanubrutinib and 10.1% of those assigned to ibrutinib had received more than three prior lines of therapy.

Over 60% of patients were aged 65 years or older and around 70% were men, with no significant differences between treatment groups.

Patients were randomized 1:1 to zanubrutinib or ibrutinib until disease progression or study withdrawal.

After a median follow-up of 15 months, the overall response rate was significantly higher with zanubrutinib than ibrutinib, at 78.3% versus 62.5% (P = .0006).

Subgroup analysis confirmed that the effect was seen regardless of age, sex, disease stage, number of prior lines of therapy, mutation status, or bulky disease.

Over a median follow-up of 14 months, the investigator-assessed 12-month PFS was 94.9% for zanubrutinib and 84.0% for ibrutinib (P = .0007). Overall survival at 12 months was 97% versus 92.7%, but the difference was not significant (P = .1081).

Patients treated with zanubrutinib experienced more grade 3 or higher adverse events than those given ibrutinib, at 55.9% versus 51.2%, although they had fewer adverse events leading to treatment discontinuation, at 7.8% versus 13.0%.

More importantly, there were fewer cardiac disorders of any grade with zanubrutinib versus ibrutinib, and any-grade atrial fibrillation was significantly less common, at 2.5% versus 10.1% (P = .0014).

Rates of hypertension and hemorrhage were similar between the two treatments, while rates of neutropenia were higher with zanubrutinib versus ibrutinib, at 28.4% versus 21.7%.

The phase 3 SEQUOIA study looked at an earlier stage of disease and included patients with previously untreated CLL/SLL (without 17p depletion) who were unsuitable for treatment with fludarabine, cyclophosphamide, and rituximab.

This trial involved 479 patients randomized to zanubrutinib or bendamustine (days 1 and 2) plus rituximab for six cycles of 28 days each (B+R).

The median age of patients was 70 years, and approximately 80% were at least 65 years old. Just over 60% were men and most (over 70%) were from Europe.

After a median of 26.2 months, independent review committee–assessed PFS was significantly longer with zanubrutinib versus B+R (hazard ratio, 0.42; P < .0001), with an estimated 24-month PFS of 85.5% versus 69.5%.

These results held whether patients were stratified by age, Binet stage, bulky disease, or 11q deletion status, and for patients with an unmutated, but not mutated, immunoglobulin heavy chain gene.

The overall response rate with zanubrutinib was 94.6% versus 85.3% with B+R, and estimated 24-month overall survival was 94.3% versus 94.6%.

Rates of adverse events of any grade were similar between the two treatment groups, although B+R was associated with a higher (grade ≥ 3) adverse event rate, at 79.7%, versus 52.5% for zanubrutinib, and a higher rate of treatment discontinuation because of adverse events, at 13.7% versus 8.3%.

Interestingly, any-grade hypertension was more common with zanubrutinib versus B+R, at 14.2% versus 10.6%, but much lower rates of neutropenia were more common with zanubrutinib, at 15.8% versus 56.8%.

The studies were sponsored by BeiGene. Dr. Hillmen has reported relationships with Janssen, AbbVie, Pharmacyclics, Roche, Gilead, AstraZeneca, SOBI, and BeiGene. Dr. Munir has reported relationships with AbbVie, AstraZeneca, Roche, Alexion, Janssen, MorphoSys, and SOBI. Other authors have also declared numerous relationships.

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

A pair of new studies offers more evidence for the value of vegetables and the risk of red meat on the cancer prevention front. Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.

The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”

Both studies were released at the annual meeting of the American Association for Cancer Research.

For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.

Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.

The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).

Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).

According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.

Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.

For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.

The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.

After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).

“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.

There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.

The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”

As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.

The authors of both studies report no relevant disclosures. No funding is reported for either study.

A pair of new studies offers more evidence for the value of vegetables and the risk of red meat on the cancer prevention front. Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.

The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”

Both studies were released at the annual meeting of the American Association for Cancer Research.

For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.

Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.

The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).

Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).

According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.

Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.

For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.

The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.

After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).

“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.

There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.

The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”

As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.

The authors of both studies report no relevant disclosures. No funding is reported for either study.

A pair of new studies offers more evidence for the value of vegetables and the risk of red meat on the cancer prevention front. Researchers report that high consumption of vegetables – especially lettuce, legumes, and cruciferous varieties – appears to lower the risk of liver cancer/liver disease. A separate team suggests that high consumption of red meat, organ meats, and processed meats boosts the risk of gastric cancer.

The findings of the latter study “reinforce the idea that avoidance of red meat and processed meat is probably good beyond [the prevention of] colorectal cancer,” said corresponding author and epidemiologist Paolo Boffetta, MD, MPH, of Stony Brook University Cancer Center, New York, in an interview. “The possible carcinogenic effect may extend beyond the colon.”

Both studies were released at the annual meeting of the American Association for Cancer Research.

For the red meat study, researchers examined statistics from the Golestan cohort study, which is prospectively tracking 50,045 people aged 40-75 from northeastern Iran. The study focuses on esophageal cancer due to the region’s high rate of the disease.

Red meat consumption is fairly rare in the region, where residents typically prefer chicken, said study lead author Giulia Collatuzzo, MD, a resident physician in occupational medicine at the University of Bologna, Italy, in an interview. On average, participants reported eating 18.4 grams daily of red meat and 72.1 grams daily of white meat.

The researchers tracked study participants for a median 12-year follow-up, during which 369 developed esophageal cancer and 368 developed gastric cancer. Red meat was only linked to more esophageal cancer in women (hazard ratio, 1.13, 95% confidence interval, 1.00-1.18, for each quintile increase in consumption).

Overall red meat consumption (including red meat, organ meat, and processed meat) was linked to higher rates of gastric cancer (HR, 1.08, 95% CI, 1.00-1.17) for each quartile increase in consumption, as was consumption of the red meat subtype alone (HR, 1.09, 95% CI, 1.00-1.18).

According to Dr. Collatuzzo, the findings suggest that those in the highest quartile of overall red meat consumption may have around a 25% increase in risk, compared with the lowest quartile.

Overall, she said, the study findings aren’t surprising. The lack of a connection between red meat consumption and esophageal cancer may be due to the fact that meat only temporarily transits through the esophagus, she said.

For the liver cancer/liver disease study, researchers examined the medical records of 470,653 subjects in the NIH-AARP Diet and Health Study. They were recruited in 1995-1996 when they were 50-71 years old. Over a median follow-up of 15.5 years, 899 developed liver cancer, and 934 died of chronic liver disease.

The median intakes of vegetables in quintile 5 (highest) and quintile 1 (lowest) were 3.7 cups daily and 1.0 cups daily, respectively, said study lead author Long-Gang Zhao, MS, a graduate student at Harvard University.

After adjusting for possible cofounders, those in the highest quintile of vegetable consumption were a third less likely to develop liver cancer, compared with the lowest quintile (HR, 0.66, 95% CI, 0.53-0.82, P < 0.01). Several types of vegetables appeared to be the strongest cancer fighters: cruciferous (broccoli, cauliflower), lettuce, legumes, and carrots. These kinds of vegetables were also linked to lower rates of chronic liver disease mortality (all P < 0.01), as was total vegetable intake for the top quintile versus the lowest quintile (HR, 0.60, 95% CI, 0.49-0.74, P = < 0.01).

“A one-cup increase (8 oz or 225 g) in vegetable intake was associated with about 20% decreased risk of liver cancer incidence and chronic liver mortality,” Zhao said.

There was no statistically significant link between fruit consumption and liver cancer or chronic liver disease mortality.

The findings provide more insight into diet and liver disease, Zhao said. “Chronic liver disease, which predisposes to liver cancer, is the tenth cause of death worldwide, causing two million deaths each year. It shares some etiological processes with liver cancer. Therefore, examining both chronic liver disease mortality and liver cancer incidence in our study may provide a more general picture for the prevention of liver diseases.”

As for limitations, both studies are based on self-reports about food consumption, which can be unreliable, and the subjects in the fruit/vegetable analysis were mainly of European origin.

The authors of both studies report no relevant disclosures. No funding is reported for either study.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

In patients with B-cell deficiencies, CoVac-1, a SARS-CoV-2 vaccine currently in clinical trials in Germany, induced T-cell immune responses in a large proportion of patients, according to study results presented at the annual meeting of the American Association for Cancer Research.

The phase 1/2 trial included 54 patients with a B-cell deficiency (mean age, 63 years; 28% female): 4 had congenital B-cell deficiency and 50 had a blood cancer (lymphocytic leukemia or lymphoma). T-cell immune responses were observed in 86% of patients 28 days after vaccination with a single CoVac-1 dose. The potency of CoVac-1–induced T-cell responses exceeded those seen typically with B cell–deficient patient responses after mRNA vaccine treatment and were comparable with those seen among nonimmunocompromised COVID-19 patients.

In the majority of individuals, currently approved SARS-CoV-2 vaccines induce a robust immune response, however, their efficacy, has been shown to be decreased among individuals who are immunocompromised. Patients treated for hematologic cancers, in particular, receive treatment regimens that damage healthy immune cells, particularly B cells, said Juliane Walz, MD, the study’s senior author and professor of medicine at University Hospital Tübingen (Germany).

“In the clinic, we see many cancer patients who do not mount sufficient humoral immune responses after vaccination with available SARS-CoV-2 vaccines,” Dr. Walz said. “These patients are at a high risk for a severe course of COVID-19.”

B-cell deficiency, she stated, can be compensated for by enhancing T-cell responses against SARS-CoV-2, which can then combat infections in the absence of neutralizing antibodies.

In a prior study of CoVac-1 among 36 adults without immune deficiency, the vaccine elicited T-cell responses that were still robust 3 months post vaccination, and that included responses against omicron and other key SARS-CoV-2 variants.

While mRNA-based or adenoviral vector-based vaccines are limited to the spike protein and are thus prone to loss of activity because of viral mutations, CoVac-1–induced T-cell immunity is far more intense and broader, Dr. Walz said.

CoVac-1 is a peptide vaccine that is injected directly rather than being encoded via mRNA and targets different viral components. It would not be given, however, to healthy, immunocompetent adults because it is important for them to have both B-cell antibody and T-cell response.

The patients with B-cell deficiency recruited for the study were given a single dose of CoVac-1 and assessed for safety and immunogenicity until day 56. Prior vaccinations with an approved SARS-CoV-2 vaccine had failed to elicit a humoral response in 87% of the subjects.

“Our vaccine does not induce antibody responses,” Dr. Walz said. “However, it could be used to induce broad T-cell responses as a complementary or additive vaccine for elderly adults. In the elderly, antibody responses decline very, very fast after vaccination.”

Dr. Walz said that CoVac-1 could find application in various syndromes associated with congenital B-cell deficiencies, in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis, or diseases treated with rituximab or other B cell–depleting therapies (for example, ofatumumab, blinatumomab, or chimeric antigen receptor T cells), and in transplant patients.

A phase 3 study of CoVac-1 versus placebo is under discussion and would require about 300-500 subjects, Dr. Walz said.

“CoVac-1 is designed to induce broad and long-lasting SARS-CoV-2 T-cell immunity, even in individuals who have impaired ability to mount sufficient immunity from a currently approved vaccine, and thus protect these high-risk patients from a severe course of COVID-19,” Dr. Walz said.

“Having an option for these patients is just critical – so this is significant work,” said Ana Maria Lopez, MD, MPH, of the Sidney Kimmel Cancer Center–Jefferson Health, Philadelphia.

Limitations of this study included the small sample size with low racial and ethnic diversity, Dr. Walz stated.

Funding was provided by the Ministry of Science, Research and the Arts of the state of Baden-Württemberg; the Federal Ministry of Research and Education in Germany; the German Research Foundation under Germany’s Excellence Strategy; and the Clinical Cooperation Unit Translational Immunology at University Hospital Tübingen. Dr. Walz holds the CoVac-1 patent.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.

More than one in seven patients with breast cancer saw their financial status deteriorate within the first years after their diagnosis, a new study found. Factors like disease severity and treatment type didn’t seem to have an impact on financial status.

The findings, presented at the annual meeting of the American Association for Cancer Research, were unexpected. “We were surprised that we did not find that patients who received more aggressive therapies were more likely to experience worsening financial concerns,” said corresponding author and medical oncologist Kathryn J. Ruddy, MD, of the Mayo Clinici in Rochester, Minn.

The study was undertaken to understand the financial stress facing patients with breast cancer. The question was whether individual or disease factors, or both, were at play.

The study is based on results from the Mayo Clinic Breast Disease Registry, a prospective cohort of patient who were at Mayo Clinic Rochester. Participants answered questions about their finances at baseline and then again at annual follow-ups.

Researchers examined survey findings from 1,957 patients (mean age 58.5, 99.1% female, 95.4% White, 54.9% bachelor degree or higher) who answered questions at least twice from 2015-2020. The average time between diagnosis and the most recent follow-up was 25.6 months.

Of the 1,957 patients, 357 (18.2%) said their finances deteriorated as measured by a 1 point or higher decline on a 10-point scale.

There was no statistically significant link between deteriorating finances and age, race, employment status, stage of cancer at diagnosis, type of cancer, or treatment type. There was a slight link between deteriorating finances and reporting that they were in the category of “pay bills, no money for special things” near diagnosis.

Other research has suggested that breast cancer may not disrupt finances to a large extent, at least early on. Earlier in 2022, Stanford (Calif.) University researchers reported the results of a survey of 273 breast and gynecologic cancer patients who were surveyed about their finances at a mean of 3.4 years after diagnosis. While one-third said their cancer caused career changes, the study described overall financial toxicity as mild.

In regard to limitations, the subject population of the new study is overwhelmingly White, and the finances were self-reported by those who participated in the survey. Also, “because our participants were recruited at a tertiary medical center, there were relatively financially secure at baseline,” Dr. Ruddy said. “More financial hardship would be expected in a more financially diverse population.”

In an interview, Cathy Bradley, PhD, associate dean for research at the University of Colorado at Denver and deputy director of the University of Colorado Cancer Center, both in Aurora, praised the study as “an important start toward assessing financial burden in the clinic. Having more universal assessments in the clinic would remove stigma.”

She cautioned about interpreting a seemingly low number of patients whose financial situation worsened. “This was for a single site where there is a high rate of health insurance either through Medicare or Medicaid. There may be some selection bias as well given that Mayo may attract a wealthier patient population. Most women completed treatment and may not have been on long-term therapies.”

Moving forward, Dr. Ruddy said, “we hope to study cost of oncologic care in more geographically and financially diverse populations with breast cancer and other cancers.”

The study was funded by the Breast Cancer Research Foundation and National Cancer Institute. The study authors and Dr. Ruddy report no relevant disclosures.

Researchers have demonstrated that diet supplementation with high-dose omega-3 fatty acids can lead to a decrease in potentially dangerous FOXA1 in benign breast tissue, potentially pointing the way toward the use of the pioneer transcription factor as a helpful biomarker for breast cancer researchers.

The findings were released at the annual meeting of the American Association for Cancer Research.

In the study, researchers who were led by Bruce F. Kimler, PhD, a radiation biologist and breast cancer researcher at the University of Kansas Medical Center, Kansas City, examined benign breast tissue cells aspirated from 12 women (mean age, 53 years; 7 on low-dose hormone replacement) before and after 6 months of high-dose omega-3 fatty acid supplementation. After the supplementation, FOXA1 positive cells fell in 11 of 12 women (P = .019). “There was a robust linear relationship between stain positivity for FOXA1 and AGR2,” the researchers reported (P < .001).

Increased FOXA1 activity along with GRHL2) transcription factor can boost endocrine resistance, while omega-3 fatty acids can reduce it.

In an interview, Robert S. Chapkin, PhD, the Allen Endowed Chair in Nutrition and Chronic Disease Prevention at Texas A&M University, College Station, said it’s important to examine the value of omega-3 fatty acid supplementation, and the understanding of biomarkers is crucial. “Omega 3 fatty acids are pleiotropic, dose dependent, and likely impact multiple signaling mechanisms in select cells types and cancer contexts. The key is to dissect out the highest impact targets and pursue them in the context of preclinical and clinical studies.”

However, he said, “in many cases, the lack of a mechanistic understanding detracts from the merit of the work.”

Studies like this are useful in the development of clinical trials to test the value of high-dose omega-3 fatty acids in breast cancer prevention trials, said Carol Fabian, MD, a breast medical oncologist with the University of Kansas Medical Center, and the study’s first author.

“They help us understand both what dose will be needed and biomarkers that will likely be helpful in predicting response. Early-phase trials with biomarker modulation as a primary endpoint are generally necessary to make sure you have the right dose for the target population prior to committing to a long-term cancer incidence study involving thousands of women and tens of millions of dollars,” she said.

What’s next? “This work was done on reserved specimens from a prior pilot trial,” Dr. Fabian said. “We need a placebo-controlled study to know for sure that omega-3 FA in a dose of about 3.2g daily, or about 2% of calories, modulates FOXA1 and/or AGR2 in postmenopausal women.”

Previously, she said, the researchers “found that high dose omega-3 administered to overweight peri- and postmenopausal high-risk women undergoing a 6-month weight loss intervention increased the number of systemic risk biomarkers which were favorably modulated compared to placebo despite the same median weight loss in each group [–10%],” Dr. Fabian said. “We want to duplicate that finding in a larger study as well as determine if omega-3 fatty acids can block tamoxifen-induced increases in AGR2 associated with endocrine resistance.”

The study was funded by the Breast Cancer Research Foundation, the Morris Family Foundation, and the University of Kansas Cancer Center. The authors and Chapkin report no relevant disclosures.

Researchers have demonstrated that diet supplementation with high-dose omega-3 fatty acids can lead to a decrease in potentially dangerous FOXA1 in benign breast tissue, potentially pointing the way toward the use of the pioneer transcription factor as a helpful biomarker for breast cancer researchers.

The findings were released at the annual meeting of the American Association for Cancer Research.

In the study, researchers who were led by Bruce F. Kimler, PhD, a radiation biologist and breast cancer researcher at the University of Kansas Medical Center, Kansas City, examined benign breast tissue cells aspirated from 12 women (mean age, 53 years; 7 on low-dose hormone replacement) before and after 6 months of high-dose omega-3 fatty acid supplementation. After the supplementation, FOXA1 positive cells fell in 11 of 12 women (P = .019). “There was a robust linear relationship between stain positivity for FOXA1 and AGR2,” the researchers reported (P < .001).

Increased FOXA1 activity along with GRHL2) transcription factor can boost endocrine resistance, while omega-3 fatty acids can reduce it.

In an interview, Robert S. Chapkin, PhD, the Allen Endowed Chair in Nutrition and Chronic Disease Prevention at Texas A&M University, College Station, said it’s important to examine the value of omega-3 fatty acid supplementation, and the understanding of biomarkers is crucial. “Omega 3 fatty acids are pleiotropic, dose dependent, and likely impact multiple signaling mechanisms in select cells types and cancer contexts. The key is to dissect out the highest impact targets and pursue them in the context of preclinical and clinical studies.”

However, he said, “in many cases, the lack of a mechanistic understanding detracts from the merit of the work.”

Studies like this are useful in the development of clinical trials to test the value of high-dose omega-3 fatty acids in breast cancer prevention trials, said Carol Fabian, MD, a breast medical oncologist with the University of Kansas Medical Center, and the study’s first author.

“They help us understand both what dose will be needed and biomarkers that will likely be helpful in predicting response. Early-phase trials with biomarker modulation as a primary endpoint are generally necessary to make sure you have the right dose for the target population prior to committing to a long-term cancer incidence study involving thousands of women and tens of millions of dollars,” she said.

What’s next? “This work was done on reserved specimens from a prior pilot trial,” Dr. Fabian said. “We need a placebo-controlled study to know for sure that omega-3 FA in a dose of about 3.2g daily, or about 2% of calories, modulates FOXA1 and/or AGR2 in postmenopausal women.”

Previously, she said, the researchers “found that high dose omega-3 administered to overweight peri- and postmenopausal high-risk women undergoing a 6-month weight loss intervention increased the number of systemic risk biomarkers which were favorably modulated compared to placebo despite the same median weight loss in each group [–10%],” Dr. Fabian said. “We want to duplicate that finding in a larger study as well as determine if omega-3 fatty acids can block tamoxifen-induced increases in AGR2 associated with endocrine resistance.”

The study was funded by the Breast Cancer Research Foundation, the Morris Family Foundation, and the University of Kansas Cancer Center. The authors and Chapkin report no relevant disclosures.

Researchers have demonstrated that diet supplementation with high-dose omega-3 fatty acids can lead to a decrease in potentially dangerous FOXA1 in benign breast tissue, potentially pointing the way toward the use of the pioneer transcription factor as a helpful biomarker for breast cancer researchers.

The findings were released at the annual meeting of the American Association for Cancer Research.

In the study, researchers who were led by Bruce F. Kimler, PhD, a radiation biologist and breast cancer researcher at the University of Kansas Medical Center, Kansas City, examined benign breast tissue cells aspirated from 12 women (mean age, 53 years; 7 on low-dose hormone replacement) before and after 6 months of high-dose omega-3 fatty acid supplementation. After the supplementation, FOXA1 positive cells fell in 11 of 12 women (P = .019). “There was a robust linear relationship between stain positivity for FOXA1 and AGR2,” the researchers reported (P < .001).

Increased FOXA1 activity along with GRHL2) transcription factor can boost endocrine resistance, while omega-3 fatty acids can reduce it.

In an interview, Robert S. Chapkin, PhD, the Allen Endowed Chair in Nutrition and Chronic Disease Prevention at Texas A&M University, College Station, said it’s important to examine the value of omega-3 fatty acid supplementation, and the understanding of biomarkers is crucial. “Omega 3 fatty acids are pleiotropic, dose dependent, and likely impact multiple signaling mechanisms in select cells types and cancer contexts. The key is to dissect out the highest impact targets and pursue them in the context of preclinical and clinical studies.”

However, he said, “in many cases, the lack of a mechanistic understanding detracts from the merit of the work.”

Studies like this are useful in the development of clinical trials to test the value of high-dose omega-3 fatty acids in breast cancer prevention trials, said Carol Fabian, MD, a breast medical oncologist with the University of Kansas Medical Center, and the study’s first author.

“They help us understand both what dose will be needed and biomarkers that will likely be helpful in predicting response. Early-phase trials with biomarker modulation as a primary endpoint are generally necessary to make sure you have the right dose for the target population prior to committing to a long-term cancer incidence study involving thousands of women and tens of millions of dollars,” she said.

What’s next? “This work was done on reserved specimens from a prior pilot trial,” Dr. Fabian said. “We need a placebo-controlled study to know for sure that omega-3 FA in a dose of about 3.2g daily, or about 2% of calories, modulates FOXA1 and/or AGR2 in postmenopausal women.”

Previously, she said, the researchers “found that high dose omega-3 administered to overweight peri- and postmenopausal high-risk women undergoing a 6-month weight loss intervention increased the number of systemic risk biomarkers which were favorably modulated compared to placebo despite the same median weight loss in each group [–10%],” Dr. Fabian said. “We want to duplicate that finding in a larger study as well as determine if omega-3 fatty acids can block tamoxifen-induced increases in AGR2 associated with endocrine resistance.”

The study was funded by the Breast Cancer Research Foundation, the Morris Family Foundation, and the University of Kansas Cancer Center. The authors and Chapkin report no relevant disclosures.

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Patients with first-episode psychosis (FEP) show altered speech patterns and content that could pinpoint symptom severity – and help predict future relapse, two new studies suggest.

In the first study, an algorithm was created to analyze speech patterns and semantic content to create novel “speech networks.” Compared with their healthy peers, patients with FEP had smaller and more fragmented networks. At-risk individuals had fragmented values that were in between those of the FEP and healthy control groups.

“This suggests that semantic speech networks can enable deeper phenotyping of formal thought disorder and psychosis,” said lead author Caroline Nettekoven, PhD, department of psychiatry, University of Cambridge, England.

In the second study, Janna N. de Boer, MD, University of Groningen, the Netherlands, and colleagues examined patients with FEP who did and did not experience relapse after 24 months of follow-up.

An algorithm based on natural language processing (NLP) of speech recordings predicted the relapses with an accuracy of more than 80%.

NLP “is a powerful tool with high potential for clinical application and diagnosis and differentiation, given its ease in acquirement, low cost, and naturally low patient burden,” said de Boer.

The findings for both studies were presented at the annual congress of the Schizophrenia International Research Society.
 

Fragmented networks

Dr. Nettekoven noted that previous research has shown “mapping the speech of a psychosis patient as a network and analyzing the network using graph theory is useful for understanding formal thought disorder.”

However, these tools ignore the semantic content of speech, which is a “key feature” that is altered in psychotic language, she added.

The researchers therefore proposed a “novel type of network to map the content of speech.”

For example, if someone said, “I see a man,” a semantic speech network developed from this sentence would have the first and last words connected by “the edge” to the word “see,” Dr. Nettekoven explained.

To explore further, the investigators developed an algorithm known as “netts” that automatically creates semantic speech networks from transcribed speech.

They first applied the algorithm to transcribed speech from a general population sample of 436 individuals and then to a clinical sample (n = 53) comprising patients with FEP, those at clinical high risk for psychosis, and a healthy control group.

Comparing the general population sample with randomly generated semantic speech networks, the investigators found that networks from the general population had fewer but larger connected components, which “reflects the nonrandom nature of speech,” said Dr. Nettekoven.

In the clinical sample, networks from the FEP group had a significantly higher number of connected components compared with the healthy control group (P = .05) and a significantly smaller median connected-component size (P < .01).

“So patients’ mental speech networks are more fragmented than those from controls,” said Dr. Nettekoven. She added that the networks from clinically high-risk individuals “showed fragmentation values in between [those of] patients and controls.”

A further clustering analysis suggested the semantic speech networks “capture a novel signal that is not already described” by other NLP measures, Dr. Nettekoven said. In addition, the network features were related to negative symptom scores and scores on the Thought and Language Index.

However, Dr. Nettekoven noted that these relationships “did not survive correcting for multiple comparisons.”
 

Relapse predictor

During her presentation of the second study, Dr. de Boer said that “predicting relapse remains challenging” in FEP.

However, she noted that recent developments in NLP have proved to be effective in a “range of applications,” including early symptom recognition and differential diagnosis in psychosis.

To determine whether NLP could help predict relapse, the study included 104 patients aged 16-55 years with FEP whose conditions had been in remission for 3-6 months. Speech recordings were made at baseline and after 3 and 6 months and were analyzed via OpenSMILE software.

After a follow-up of 24 months, 24 of the patients remaining in the study had not experienced relapse, while 21 patients had experienced relapse. There were no significant age, education, or gender differences between those who did and those who did not experience relapse.

On the basis of speech analysis, the investigators identified a machine learning classifier, which showed an accuracy of 80.8% in predicting relapse 3 months in advance of the occurrence.
 

‘Valid and informative’

Commenting on the studies, Eric J. Tan, PhD, Centre for Mental Health, Swinburne University of Technology, Melbourne, said they are “but two of a variety of ways in which speech can be analyzed and are both equally valid and informative.”

The key takeaway “is that both studies are examples of the ways in which speech can be used clinically, such as for predicting relapse and for the potential proxy measure for the assessment of symptom severity,” said Dr. Tan, who was not involved with the research.

The studies also show that “speech is sensitive to different stages of the disorder, as well as its individual symptoms,” he added.

However, Dr. Tan noted that although “speech may be more of a sign of an underlying pathology or dysfunction, given that it waxes and wanes with illness severity, more analyses are needed before drawing definitive conclusions.” This is especially needed “given the relative infancy of quantitative speech analysis,” he said.

“It would also be useful to conduct these analyses across a variety of different languages to look for commonalities and differences that will help shed light on the variables most closely linked to the disorder,” Dr. Tan concluded.

The investigators have reported no relevant financial relationships. Dr. Tan has received an Early Career Research Fellowship from the National Health and Medical Research Council of Australia.

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

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

courtesy MSKCC, New York

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

courtesy MSKCC, New York

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Physicians treating Hodgkin lymphoma should not delay potentially curative allogeneic hematopoietic cell transplantation (allo-HCT) over fears of checkpoint inhibitor (CPI)–related graft-versus-host disease (GVHD), said a speaker at the annual meeting European Society for Blood and Bone Marrow Transplantation.

In fact, prior treatment with PD-1–directed therapies nivolumab (Opdivo) and pembrolizumab (Keytruda) appears to improve outcomes in allo-HCT patients, said Miguel-Angel Perales, MD, chief of the adult bone marrow transplant service at Memorial Sloan Kettering Cancer Center in New York. 

“The use of allogeneic HCT is decreasing for Hodgkin even though it is a curative option, and we see patients referred after they have had multiple lines of therapy,” Dr. Perales said in an interview. “The lymphoma MDs have a perception that outcomes are poor, and therefore don’t refer.”

courtesy MSKCC, New York

To illustrate his point, Dr. Perales shared data from the EBMT database. In 2014, the registry accrued approximately 450 allo-HCT cases; by 2021 this had fallen to fewer than 200 procedures.

Ironically, this declining enthusiasm for transplantation coincides with a steady improvement in transplant outcomes following PD-1 blockade, Dr. Perales noted. For example, an analysis, published in Nature, yielded an 82% overall survival (OS) at 3 years in patients who underwent allo-HCT after CPI treatment (n =209).

“Results of allo-HCT in patients with Hodgkin show a remarkable cure rate,” said Dr. Perales. “Part of that is probably driven by lower relapse due to enhanced graft-versus-lymphoma effect due to long CPI half-life.” (The half-lives of pembrolizumab and nivolumab are 22 and 25 days, respectively.)

At the EBMT meeting, Dr. Perales presented a new retrospective analysis that tested the hypothesis that CPIs might actually improve outcomes for allo-HCT patients. An international team of clinicians from EBMT and the Center for International Blood and Marrow Transplant Research (CIBMTR) compared allo-HCT outcomes with (n = 347) and without (n = 1,382) prior treatment with a checkpoint inhibitor. 

They found that prior CPI therapy was, indeed, associated with lower relapse (hazard ratio, 0.53; P = .00023) and longer progression-free survival (PFS) (HR, 0.75; P = .0171).

However, prior PD-1 drugs provided no survival advantage, Dr. Perales said. “The easiest explanation for a study showing a difference in PFS/relapse, not OS, is that we have good treatments that can treat patients who relapse and so their overall survival ends up being the same.”

The researchers also confirmed previous reports that patients who received PD-1 inhibitors prior to transplant had a higher incidence of GVHD. Prevalence of acute grades 2-4 GVHD was significantly higher (P = .027); however, acute grades 3-4 GVHD and chronic GVHD were not significantly different between the two groups.

Dr. Perales speculated that the use of posttransplant cyclophosphamide for GVHD prophylaxis would mitigate the risk of GVHD associated with PD-1 inhibitors, “we have not yet proven that formally ... [we] are still analyzing our data.”

Commenting on the results of the new analysis, Dr. Perales expressed concern that patients are being recruited to early-phase clinical trials after failing on a checkpoint inhibitor, instead of being offered allo-HCT – a potentially curative treatment – because treaters are misinformed about the safety of transplant after these drugs.

The NIH clinical-trials database backs up Dr. Perales’ worries. In the United States, for example, there are currently 19 trials recruiting for relapsed/refractory Hodgkin lymphoma patients prior to transplant. Of these, 15 studies permit enrollment of patients who have failed on CPIs, and 8 are phase 1 or 2 studies.

“The good news is that new drugs, including CPIs, have dramatically changed outcomes in this disease and that fewer patients now need an allo-HCT,” said Dr. Perales. And if a transplant is needed, “it is safe to perform allo-HCT in patients treated with prior CPI.” 

However, time is of the essence. “Patients with Hodgkin lymphoma should be referred to allo-HCT if they are not responding or tolerating CPI, rather than go on a series of phase 1 trials,” Dr. Perales said. “Median age is 32, and we should be going for a cure, nothing less.” 

Dr. Perales reported receiving honoraria from numerous pharmaceutical companies; serving on the data and safety monitoring boards of Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier; and serving on the scientific advisory board of NexImmune. He has ownership interests in NexImmune and Omeros, and has received institutional research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
 

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
 

An increase in body weight appears to have a detrimental effect on some radiographic features of knee, but not hip, osteoarthritis, researchers reported at the OARSI 2022 World Congress.

Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)

Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.

Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).

Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).

Importance of weight change in OA

“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.

“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”

He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
 

Why look at weight change effects in OA?

“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.

Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.

The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.

“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.

Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.

The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.

“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”

Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”

There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.

Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.

“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”

The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.