Hematology News

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

At first glance, hematologists may not seem like they’d be likely to get urgent calls from the emergency department at 3 a.m. After all, they typically work during normal business hours. However, severe medical crises in blood-cancer patients can occur, and drowsy hematologists may find themselves providing guidance to emergency physicians about how to deal with rapidly deteriorating patients.

When a patient with a blood-cancer crisis comes in, “I can recognize what’s going on, and I can initiate treatment. But if you do have a true hematologic emergency, then you need a hematologist to be able to contribute to your care,” Molly Estes, MD, an emergency physician with California’s Loma Linda University, said in an interview.

In situations such as a patient with an extraordinarily high white blood count, “you’ll be calling your hematologist for treatment recommendations and calling your nephrologist for assistance managing electrolyte disorders,” Megan Boysen-Osborn, MD, an emergency physician with the University of California at Irvine, said in an interview.

Here’s a look at three emergency hematologic conditions that lead to late-night phone calls:
 

Leukocytosis

Blood cancers can cause white blood cell counts to skyrocket, a condition known as leukocytosis, but a high count is not necessarily an emergency. The key is to figure out whether the high count is normal for the patient — perhaps due to the disease or the medical treatment — or a sign of an internal medical crisis, Dr. Estes said.

“Let’s say you stubbed your toe in the night, and I happened to get blood work on you and incidentally notice that your white blood cells are high. But they’re the same high level that they always are,” Dr. Estes said. “That’s a completely different scenario than if I’m seeing you for fever, vomiting, and stomach pain.”

Indeed, there’s no cut-off that differentiates a dangerously high white blood count from one that’s acceptable, Mikkael A. Sekeres, MD, MS, chief of hematology at Sylvester Comprehensive Cancer Center at the University of Miami Health System, said in an interview.

“In the past, I’ve taken care of a couple of patients who had chronic lymphocytic leukemia and white blood cell counts that were 200,000 or 300,000 [white blood cells per microliter] and worked out in the gym every day,” he said. “It didn’t negatively affect them. On the flip side, I have also taken care of patients with acute myeloid leukemia with a white blood cell count of 50,000. That landed them in the intensive care unit.”

Dr. Estes said that her first impulse in cases of high white blood cell count is to give IV fluids to dilute the blood and prevent the cells from turning blood into sludge via hyperviscosity syndrome. Dr. Sekeres said this makes sense, since the condition can lead to blockages in vessels and cause heart attacks and strokes.

There are other options, depending on the severity of the case. Hydroxyurea can be administered to lower white blood cell counts along with allopurinol to protect the kidneys, Dr. Sekeres said. In some situations, he said, “we’ll consider initiating chemotherapy immediately to reduce the level of the white blood cells. Or we will consider placing a patient on dialysis to take off some of those white blood cells.”
 

Tumor lysis syndrome

While it’s rare, tumor lysis syndrome can occur when tumors release their content into blood stream. According to Dr. Sekeres, this can happen when “cancers that grow so quickly that they can start to outgrow their own blood supply and start dying before we even treat patients. When this happens, it causes electrolyte disarray.”

It’s crucial to understand the potential for patients to quickly get worse, he said. He advises clinicians to aggressively check lab values for electrolyte abnormalities and aggressively administer IV fluids and electrolyte replacement when needed. “It’s also important to let the intensive care unit know that they may need to be activated,” he said. Fortunately, he noted, patients can often be stabilized.
 

Differentiation syndrome

According to the Cleveland Clinic, medications used to treat acute myeloid leukemia and acute promyelocytic leukemia cause cancer cells to differentiate from immature states to mature normal states. But the process can go awry when fluid leaks out of blood vessels in a condition called differentiation syndrome. This can cause multiple problems, Dr. Sekeres said.

A 2020 report noted the potential for “acute end-organ damage with peripheral edema, hypotension, acute renal failure, and interstitial pulmonary infiltrates.”

In these cases, aggressive supportive management is key, Dr. Sekeres said. If a patient is having difficulty breathing, for example, they’ll need electrolyte management and perhaps support via a respirator, he said.

“Most people with acute promyelocytic leukemia can fully recover from differentiation syndrome with prompt, effective treatment,” the Cleveland Clinic notes. It adds that the disease is “highly curable.”

In all of these emergent crises, Dr. Sekeres said, it’s important for hematologists understand that “patients can get very sick very quickly,” and it’s important to intervene early and often.

Dr. Sekeres serves on advisory boards for BMS and Curium Pharma. Dr. Estes and Dr. Boysen-Osborn have no disclosures.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

A review of the federal Open Payments database found that the pharmaceutical and medical device industry paid physicians $12.1 billion over nearly a decade.

Almost two thirds of eligible physicians — 826,313 doctors — received a payment from a drug or device maker from 2013 to 2022, according to a study published online in JAMA on March 28. Overall, the median payment was $48 per physician.

Orthopedists received the largest amount of payments in aggregate, $1.3 billion, followed by neurologists and psychiatrists at $1.2 billion and cardiologists at $1.29 billion.

Geriatric and nuclear medicine specialists and trauma and pediatric surgeons received the least amount of money in aggregate, and the mean amount paid to a pediatric surgeon in the top 0.1% was just $338,183 over the 9-year study period.

Excluding 2013 (the database was established in August that year), the total value of payments was highest in 2019 at $1.6 billion, up from $1.34 billion in 2014. It was lowest in 2020, the peak year of the COVID-19 pandemic, but dipped to $864 billion that year and rebounded to $1.28 billion in 2022, wrote the authors.

The Open Payments database, administered by the Centers for Medicare & Medicaid Services, requires drug and device makers and group purchasing organizations to report payments made to physicians, including for consulting services, speaking fees, food and beverages, travel and lodging, education, gifts, grants, and honoraria.

The database was created to shed light on these payments, which have been linked in multiple studies to more prescribing of a particular drug or more use of a particular device.

The JAMA review appeared to show that with the exception of the pandemic year, the relationships have more or less stayed the same since Open Payments began.

“There’s been no sea change, no massive shift in how these interactions are happening,” said Deborah C. Marshall, MD, assistant professor in the Department of Radiation Oncology at the Icahn School of Medicine at Mount Sinai in New York City, who has studied industry payments.

“There’s no suggestion that anything is really changing other than that’s there is transparency,” said Robert Steinbrook, MD, director of the Health Research Group at Public Citizen.

Still, Dr. Steinbrook told this news organization, “it’s better to know this than to not know this.”

The unchanging nature of industry-physician relationships “suggests that to reduce the volume and magnitude of payments, more would need to be done,” he said.

“Really, this should be banned. Doctors should not be allowed to get gifts from pharmaceutical companies,” said Adriane Fugh-Berman, MD, professor of pharmacology and physiology at Georgetown University, and director of PharmedOut, a Georgetown-based project that advances evidence-based prescribing and educates healthcare professionals about pharmaceutical marketing practices.

“The interactions wouldn’t be happening unless there was a purpose for them,” said Dr. Marshall. The relationships are “built with intention,” Dr. Marshall told this news organization.
 

Top Earners Range From $195,000 to $4.8 Million

Payments to the median physician over the study period ranged from $0 to $2339, but the mean payment to top earners — those in the top 0.1% — ranged from $194,933 for hospitalists to $4.8 million for orthopedic specialists.

Overall, the median payment was $48 per physician.

But small dollar amounts should not be discounted — even if it’s just a $25-catered lunch — said Aaron Mitchell, MD, a medical oncologist and assistant attending physician at Memorial Sloan Kettering Cancer Center in New York City who has studied industry-physician relationships. “The influence is not just in the dollar value,” Dr. Mitchell told this news organization. “It’s about the time listening to and the time in personal contact with industry representatives that these dollars are a marker for,” he said.

“There’s no such thing as a free lunch,” agreed Dr. Marshall. It’s “pretty well established” that lower-value payments do have influence, which is why academic institutions have established policies that limit gifts and meals and other payments from industry, she said.

Dr. Fugh-Berman said, “the size of the gift doesn’t really matter,” adding that research she conducted had shown that “accepting a meal increased not only the expense of the prescriptions that Medicare physicians wrote but also the number of prescriptions.”
 

Payments Mostly for High-Dollar Products

The top 25 drugs and devices that were related to industry payments tended to be high-cost brand-name products.

The top drug was Janssen’s Xarelto, an anticoagulant first approved in 2011 that costs about $600 a month, according to GoodRx. The drug has had annual sales of $4-$6 billion.

Xarelto was followed by Eliquis, another anticoagulant; Humira, used for a variety of autoimmune conditions including plaque psoriasis, rheumatoid arthritis, Crohn’s disease, and ulcerative colitis; Invokana, Jardiance, and Farxiga, all for type 2 diabetes.

The top medical devices included the da Vinci Surgical System, Mako SmartRobotics, CoreValve Evolut, Natrelle Implants, and Impella, a heart pump that received a US Food and Drug Administration (FDA) warning that it was associated with a heightened risk for death.
 

Industry Influence May Lead to Higher Cost, Poor Quality Care

Multiple studies have shown that payments to physicians tend to lead to increased prescribing and, often, higher costs for Medicare, a health system, or patients.

“I’m sure there are still a lot of physicians out there who think they’re getting away with something, that they can take meals, or they can take consulting fees and not be influenced, but there’s overwhelming data showing that it always influences you,” said Dr. Fugh-Berman.

One study in 2020 that used the Open Payments database found that physicians increase prescribing of the drugs for which they receive payment in the months just after the payment. The authors also showed that physicians who are paid prescribe lower-quality drugs following the payment, “although the magnitude is small and unlikely to be clinically significant.”

Dr. Marshall said that more studies are needed to determine whether quality of care is being affected when a physician prescribes a drug after an industry payment.

For now, there seems to be little appetite among physicians to give up the payments, said Dr. Marshall and others.

Physicians in some specialties see the payments as “an implicit statement about their value,” said Dr. Marshall.

In oncology, having received a lot of payments “gets worn more as a badge of honor,” said Dr. Mitchell.

The clinicians believe that “by collaborating with industry we are providing scientific expertise to help develop the next generation of technology and cures,” Dr. Mitchell said, adding that they see the payments “as a mark of their impact.”

Among the JAMA study authors, Joseph S. Ross, MD, reported that he is a deputy editor of JAMA but was not involved in decisions regarding acceptance of the manuscript or its review. Dr. Ross also reported receiving grants from the FDA, Johnson and Johnson, the Medical Devices Innovation Consortium, the Agency for Healthcare Research and Quality, and the National Heart, Lung, and Blood Institute. He was an expert witness in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled in 2022. Dr. Steinbrook, Dr. Marshall, and Dr. Mitchell reported no relevant financial relationships. Dr. Fugh-Berman reported being an expert witness for plaintiffs in complaints about drug and device marketing practices.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I’m going to tell you about a chemical that might cause cancer — one I suspect you haven’t heard of before.

These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.

So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.

PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.

But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.

PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.

This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.

What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.

In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.

In other words, we can’t prove they’re cancerous — but come on, they probably are.

Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).

Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.

The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.

Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.

This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.

This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.

After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.

Dr. Wilson

Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved danicopan (Voydeya, AstraZeneca) as an add-on therapy to treat extravascular hemolysis in adults receiving ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH), according to a press release from AstraZeneca.

PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.

Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.

Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.

Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.

Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.

Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.

Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved danicopan (Voydeya, AstraZeneca) as an add-on therapy to treat extravascular hemolysis in adults receiving ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH), according to a press release from AstraZeneca.

PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.

Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.

Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.

Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.

Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.

Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.

Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved danicopan (Voydeya, AstraZeneca) as an add-on therapy to treat extravascular hemolysis in adults receiving ravulizumab or eculizumab for paroxysmal nocturnal hemoglobinuria (PNH), according to a press release from AstraZeneca.

PNH is a rare blood disorder affecting 1-10 individuals per million. The condition, which eliminates red blood cells and leads to blood clots and impaired bone marrow function, can cause life-threatening anemia, thrombosis, and bone marrow dysfunction. About half of people with the condition die from thrombotic complications.

Ravulizumab and eculizumab, also both made by AstraZeneca, inhibit the destruction of red blood cells. However, 10%-20% of patients treated with the antibody infusions experience significant extravascular hemolysis, in which these surviving red blood cells are eliminated by the spleen and liver. Extravascular hemolysis can lead to ongoing anemia, which can lead patients to require blood transfusions.

Danicopan, an investigational, first-in-class, oral complement factor D inhibitor, is designed to control intravascular hemolysis and prevent extravascular hemolysis.

Approval of the oral medication was based on the phase 3 ALPHA trial in 63 patients with PNH who received ravulizumab or eculizumab and experienced significant extravascular hemolysis. These patients were randomized 2:1 to either danicopan or placebo.

Danicopan add-on significantly improved hemoglobin concentrations at 12 weeks (least squares mean improvement from baseline: 2.94 g/dL with danicopan vs 0.50 g/dL with placebo) and made transfusions less likely.

Headache, nausea, arthralgia, and diarrhea were the most common treatment-emergent side effects. Serious adverse events in the danicopan group included cholecystitis and COVID-19 in one patient each.

Danicopan carries a boxed warning of serious infections and is available only through a Risk Evaluation and Mitigation Strategy program.

A version of this article appeared on Medscape.com.

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

Electronic health records (EHRs) make providing coordinated, efficient care easier and reduce medical errors and test duplications; research has also correlated EHR adoption with higher patient satisfaction and outcomes. However, for physicians, the benefits come at a cost.

Physicians spend significantly more time in healthcare portals, making notes, entering orders, reviewing clinical reports, and responding to patient messages.

“I spend at least the same amount of time in the portal that I do in scheduled clinical time with patients,” said Eve Rittenberg, MD, primary care physician at Brigham and Women’s Hospital and assistant professor at Harvard Medical School, Boston. “So, if I have a 4-hour session of seeing patients, I spend at least another 4 or more hours in the patient portal.”

The latest data showed that primary care physicians logged a median of 36.2 minutes in the healthcare portal per patient visit, spending 58.9% more time on orders, 24.4% more time reading and responding to messages, and 13% more time on chart review compared with prepandemic portal use.

“EHRs can be very powerful tools,” said Ralph DeBiasi, MD, a clinical cardiac electrophysiologist at Yale New Haven Health in Connecticut. “We’re still working on how to best harness that power to make us better doctors and better care teams and to take better care of our patients because their use can take up a lot of time.”
 

Portal Time Isn’t Paid Time

Sharp increases in the amount of time spent in the EHR responding to messages or dispensing medical advice via the portal often aren’t linked to increases in compensation; most portal time is unpaid.

“There isn’t specific time allocated to working in the portal; it’s either done in the office while a patient is sitting in an exam room or in the mornings and evenings outside of traditional working hours,” Dr. DeBiasi told this news organization. “I think it’s reasonable to consider it being reimbursed because we’re taking our time and effort and making decisions to help the patient.”

Compensation for portal time affects all physicians, but the degree of impact depends on their specialties. Primary care physicians spent significantly more daily and after-hours time in the EHR, entering notes and orders, and doing clinical reviews compared to surgical and medical specialties.

In addition to the outsized impact on primary care, physician compensation for portal time is also an equity issue.

Dr. Rittenberg researched the issue and found a higher volume of communication from both patients and staff to female physicians than male physicians. As a result, female physicians spend 41.4 minutes more on the EHR than their male counterparts, which equates to more unpaid time. It’s likely no coincidence then that burnout rates are also higher among female physicians, who also leave the clinical workforce in higher numbers, especially in primary care.

“Finding ways to fairly compensate physicians for their work also will address some of the equity issues in workload and the consequences,” Dr. Rittenberg said.
 

Addressing the Issue

Some health systems have started charging patients who seek medical advice via patient portals, equating the communication to asynchronous acute care or an additional care touch point and billing based on the length and complexity of the messages. Patient fees for seeking medical advice via portals vary widely depending on their health system and insurance.

At University of California San Francisco Health, billing patients for EHR communication led to a sharp decrease in patient messages, which eased physician workload. At Cleveland Clinic, physicians receive “productivity credits” for the time spent in the EHR that can be used to reduce their clinic hours (but have no impact on their compensation).

Changes to the Medicare Physician Fee Schedule also allow physicians to bill for “digital evaluation and management” based on the time spent in an EHR responding to patient-initiated questions and requests.

However, more efforts are needed to ease burnout and reverse the number of physicians who are seeing fewer patients or leaving medical practice altogether as a direct result of spending increasing amounts of unpaid time in the EHR. Dr. Rittenberg, who spends an estimated 50% of her working hours in the portal, had to reduce her clinical workload by 25% due to such heavy portal requirements.

“The workload has become unsustainable,” she said. “The work has undergone a dramatic change over the past decade, and the compensation system has not kept up with that change.”
 

Prioritizing Patient and Physician Experiences

The ever-expanding use of EHRs is a result of their value as a healthcare tool. Data showed that the electronic exchange of information between patients and physicians improves diagnostics, reduces medical errors, enhances communication, and leads to more patient-centered care — and physicians want their patients to use the portal to maximize their healthcare.

“[The EHR] is good for patients,” said Dr. DeBiasi. “Sometimes, patients have access issues with healthcare, whether that’s not knowing what number to call or getting the right message to the right person at the right office. If [the portal] is good for them and helps them get access to care, we should embrace that and figure out a way to work it into our day-to-day schedules.”

But maximizing the patient experience shouldn’t come at the physicians’ expense. Dr. Rittenberg advocates a model that compensates physicians for the time spent in the EHR and prioritizes a team approach to rebalance the EHR workload to ensure that physicians aren’t devoting too much time to administrative tasks and can, instead, focus their time on clinical tasks.

“The way in which we provide healthcare has fundamentally shifted, and compensation models need to reflect that new reality,” Dr. Rittenberg added.

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

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Despite concerns about malpractice risk among physicians, investigators found no successful malpractice litigation related to active surveillance as a management strategy for low-risk cancers.

METHODOLOGY:

• Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
• Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and  or  from 1990 to 2022.
• Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
• Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.

TAKEAWAY:

• Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
• In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
• The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
• No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.

IN PRACTICE:

“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”

SOURCE:

This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.

LIMITATIONS:

The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.

DISCLOSURES:

The researchers did not provide any disclosures.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE: 

“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines. Optimizing vaccination status includes ensuring patients and household members receive recommended vaccines and adjusting this strategy depending on patients’ underlying immune status and their anticancer therapy.

METHODOLOGY: 

• “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote. 
• The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts. 
• The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies. 
• Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies. 
• The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer. 

TAKEAWAY:

• The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment. 
• The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT. 
• After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months. 
• After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines. 
• Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe. 

IN PRACTICE:

“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”

SOURCE:

Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.

LIMITATIONS:

The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.

DISCLOSURES:

This research had no commercial funding. Disclosures for the guideline panel are available with the original article.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.