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Immunotherapy May Be Overused in Dying Patients With Cancer
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Chemotherapy has fallen out of favor for treating cancer toward the end of life. The toxicity is too high, and the benefit, if any, is often too low.
Immunotherapy, however, has been taking its place.
This means “there are patients who are getting immunotherapy who shouldn’t,” said Yale University, New Haven, Connecticut, surgical oncologist Sajid Khan, MD, senior investigator on a recent study that highlighted the growing use of these agents in patients’ last month of life.
What’s driving this trend, and how can oncologists avoid overtreatment with immunotherapy at the end of life?
The N-of-1 Patient
With immunotherapy at the end of life, “each of us has had our N-of-1” where a patient bounces back with a remarkable and durable response, said Don Dizon, MD, a gynecologic oncologist at Brown University, Providence, Rhode Island.
He recalled a patient with sarcoma who did not respond to chemotherapy. But after Dr. Dizon started her on immunotherapy, everything turned around. She has now been in remission for 8 years and counting.
The possibility of an unexpected or remarkable responder is seductive. And the improved safety of immunotherapy over chemotherapy adds to the allure.
Meanwhile, patients are often desperate. It’s rare for someone to be ready to stop treatment, Dr. Dizon said. Everybody “hopes that they’re going to be the exceptional responder.”
At the end of the day, the question often becomes: “Why not try immunotherapy? What’s there to lose?”
This thinking may be prompting broader use of immunotherapy in late-stage disease, even in instances with no Food and Drug Administration indication and virtually no supportive data, such as for metastatic ovarian cancer, Dr. Dizon said.
Back to Earth
The problem with the hopeful approach is that end-of-life turnarounds with immunotherapy are rare, and there’s no way at the moment to predict who will have one, said Laura Petrillo, MD, a palliative care physician at Massachusetts General Hospital, Boston.
Even though immunotherapy generally comes with fewer adverse events than chemotherapy, catastrophic side effects are still possible.
Dr. Petrillo recalled a 95-year-old woman with metastatic cancer who was largely asymptomatic.
She had a qualifying mutation for a checkpoint inhibitor, so her oncologist started her on one. The patient never bounced back from the severe colitis the agent caused, and she died of complications in the hospital.
Although such reactions with immunotherapy are uncommon, less serious problems caused by the agents can still have a major impact on a person’s quality of life. Low-grade diarrhea, for instance, may not sound too bad, but in a patient’s daily life, it can translate to six or more episodes a day.
Even with no side effects, prescribing immunotherapy can mean that patients with limited time left spend a good portion of it at an infusion clinic instead of at home. These patients are also less likely to be referred to hospice and more likely to be admitted to and die in the hospital.
And with treatments that can cost $20,000 per dose, financial toxicity becomes a big concern.
In short, some of the reasons why chemotherapy is not recommended at the end of life also apply to immunotherapy, Dr. Petrillo said.
Prescribing Decisions
Recent research highlights the growing use of immunotherapy at the end of life.
Dr. Khan’s retrospective study found, for instance, that the percentage of patients starting immunotherapy in the last 30 days of life increased by about fourfold to fivefold over the study period for the three cancers analyzed — stage IV melanoma, lung, and kidney cancers.
Among the population that died within 30 days, the percentage receiving immunotherapy increased over the study periods — 0.8%-4.3% for melanoma, 0.9%-3.2% for NSCLC, and 0.5%-2.6% for kidney cell carcinoma — prompting the conclusion that immunotherapy prescriptions in the last month of life are on the rise.
Prescribing immunotherapy in patients who ultimately died within 1 month occurred more frequently at low-volume, nonacademic centers than at academic or high-volume centers, and outcomes varied by practice setting.
Patients had better survival outcomes overall when receiving immunotherapy at academic or high-volume centers — a finding Dr. Khan said is worth investigating further. Possible explanations include better management of severe immune-related side effects at larger centers and more caution when prescribing immunotherapy to “borderline” candidates, such as those with several comorbidities.
Importantly, given the retrospective design, Dr. Khan and colleagues already knew which patients prescribed immunotherapy died within 30 days of initiating treatment.
More specifically, 5192 of 71,204 patients who received immunotherapy (7.3%) died within a month of initiating therapy, while 66,012 (92.7%) lived beyond that point.
The study, however, did not assess how the remaining 92.7% who lived beyond 30 days fared on immunotherapy and the differences between those who lived less than 30 days and those who survived longer.
Knowing the outcome of patients at the outset of the analysis still leaves open the question of when immunotherapy can extend life and when it can’t for the patient in front of you.
To avoid overtreating at the end of life, it’s important to have “the same standard that you have for giving chemotherapy. You have to treat it with the same respect,” said Moshe Chasky, MD, a community medical oncologist with Alliance Cancer Specialists in Philadelphia, Pennsylvania. “You can’t just be throwing” immunotherapy around “at the end of life.”
While there are no clear predictors of risk and benefit, there are some factors to help guide decisions.
As with chemotherapy, Dr. Petrillo said performance status is key. Dr. Petrillo and colleagues found that median overall survival with immune checkpoint inhibitors for advanced non–small cell lung cancer was 14.3 months in patients with an Eastern Cooperative Oncology Group performance score of 0-1 but only 4.5 months with scores of ≥ 2.
Dr. Khan also found that immunotherapy survival is, unsurprisingly, worse in patients with high metastatic burdens and more comorbidities.
“You should still consider immunotherapy for metastatic melanoma, non–small cell lung cancer, and renal cell carcinoma,” Dr. Khan said. The message here is to “think twice before using” it, especially in comorbid patients with widespread metastases.
“Just because something can be done doesn’t always mean it should be done,” he said.
At Yale, when Dr. Khan works, immunotherapy decisions are considered by a multidisciplinary tumor board. At Mass General, immunotherapy has generally moved to the frontline setting, and the hospital no longer prescribes checkpoint inhibitors to hospitalized patients because the cost is too high relative to the potential benefit, Dr. Petrillo explained.
Still, with all the uncertainties about risk and benefit, counseling patients is a challenge. Dr. Dizon called it “the epitome of shared decision-making.”
Dr. Petrillo noted that it’s critical not to counsel patients based solely on the anecdotal patients who do surprisingly well.
“It’s hard to mention that and not have that be what somebody anchors on,” she said. But that speaks to “how desperate people can feel, how hopeful they can be.”
Dr. Khan, Dr. Petrillo, and Dr. Chasky all reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
SUNY Downstate Emergency Medicine Doc Charged With $1.5M Fraud
In a case that spotlights the importance of comprehensive financial controls in medical offices,
Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”
Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.
Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.
The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.
“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.
SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.
Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
Size of Alleged Theft Is ‘Very Unusual’
David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”
William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).
Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).
The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
Even Small Medical Offices Can Act to Prevent Fraud
What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”
Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”
One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
A version of this article first appeared on Medscape.com.
In a case that spotlights the importance of comprehensive financial controls in medical offices,
Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”
Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.
Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.
The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.
“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.
SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.
Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
Size of Alleged Theft Is ‘Very Unusual’
David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”
William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).
Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).
The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
Even Small Medical Offices Can Act to Prevent Fraud
What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”
Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”
One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
A version of this article first appeared on Medscape.com.
In a case that spotlights the importance of comprehensive financial controls in medical offices,
Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”
Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.
Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.
The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.
“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.
SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.
Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
Size of Alleged Theft Is ‘Very Unusual’
David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”
William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).
Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).
The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
Even Small Medical Offices Can Act to Prevent Fraud
What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”
Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”
One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
A version of this article first appeared on Medscape.com.
FDA Approves First Engineered Cell Therapy for a Solid Tumor
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
Afami-cel — the first engineered cell therapy for a solid tumor — is indicated specifically for adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive for several human leukocyte antigens (HLAs), and whose tumors express melanoma-associated antigen A4, as determined by FDA-authorized companion diagnostic devices.
The single-dose treatment targets solid tumors expressing melanoma-associated antigen A4, a protein highly expressed in synovial sarcoma.
Synovial sarcoma is a rare form of cancer, which affects about 1000 people in the US each year. Malignant cells develop and form a tumor in soft tissues, often in the extremities.
“Adults with metastatic synovial sarcoma, a life-threatening form of cancer, often face limited treatment options in addition to the risk of cancer spread or recurrence,” Nicole Verdun, MD, director of the Office of Therapeutic Products in the FDA’s Center for Biologics Evaluation and Research, said in the agency press release announcing the approval. “Today’s approval represents a significant milestone in the development of an innovative, safe and effective therapy for patients with this rare but potentially fatal disease.”
T-cell receptor therapy, like chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, involves altering patient T cells to fight cancer. While CAR-T therapy inserts an artificial receptor to target a specific surface protein on cancer cells, the T-cell receptor therapy modifies existing receptors to recognize an array of antigens on the surface of cancer cells — a promising strategy for targeting solid tumors.
The accelerated approval of afami-cel was based on the phase 2 SPEARHEAD-1 trial in 44 patients with synovial sarcoma who received a single infusion of the therapy. The trial had enrolled 52 patients, but 8 did not receive afami-cel, including 3 who died and 1 who withdrew.
According to the FDA announcement, the overall response rate was 43.2%, with a median time to response of 4.9 weeks. The median duration of response was 6 months (95% CI, 4.6 months to not reached). Among patients who responded, 39% had a duration of response of 12 months or longer.
“These results suggest that a one-time treatment with afami-cel has the potential to extend life while allowing responders to go off chemotherapy,” said lead investigator Sandra D’Angelo, MD, a sarcoma specialist at Memorial Sloan Kettering Cancer Center in New York City, in a company press release.
The prescribing information includes a boxed warning for serious or fatal cytokine release syndrome.
The most common nonlaboratory adverse reactions, occurring in at least 20% of patients, included cytokine release syndrome, nausea, vomiting, fatigue, infections, pyrexia, constipation, dyspnea, tachycardia, hypotension, diarrhea, and edema. The most common grade 3 or 4 laboratory abnormalities, occurring in at least 20% of patients, included decreased lymphocyte count, neutrophil count, white cell blood count, red blood cell, and platelet count.
The recommended dose is between 2.68x109 to 10x109 MAGE-A4 T-cell receptor–positive T-cells. The FDA notice specifies not using a leukodepleting filter or prophylactic systemic corticosteroids.
The list price for the one-time therapy is $727,000, according to Fierce Pharma.
A version of this article first appeared on Medscape.com.
FDA Expands Darzalex Faspro Indication in Myeloma
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article first appeared on Medscape.com.
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article first appeared on Medscape.com.
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article first appeared on Medscape.com.
The Last 30 Days: How Oncologists’ Choices Affect End-of-Life Cancer Care
TOPLINE:
Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.
METHODOLOGY:
- Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
- A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
- Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
- The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
- Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.
TAKEAWAY:
- Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
- Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
- Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
- No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).
IN PRACTICE:
“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.
SOURCE:
The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.
LIMITATIONS:
The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.
DISCLOSURES:
The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.
METHODOLOGY:
- Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
- A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
- Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
- The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
- Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.
TAKEAWAY:
- Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
- Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
- Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
- No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).
IN PRACTICE:
“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.
SOURCE:
The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.
LIMITATIONS:
The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.
DISCLOSURES:
The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.
METHODOLOGY:
- Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
- A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
- Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
- The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
- Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.
TAKEAWAY:
- Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
- Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
- Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
- No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).
IN PRACTICE:
“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.
SOURCE:
The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.
LIMITATIONS:
The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.
DISCLOSURES:
The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Ancient Viruses in Our DNA Hold Clues to Cancer Treatment
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.
The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)
Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.
But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.
Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.
Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.
Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.
The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.
Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.
“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”
Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.
The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.
Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.
“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.
“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.
“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.
Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.
More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
A version of this article first appeared on Medscape.com.
FROM SCIENCE ADVANCES
FDA Expands Darzalex Faspro Indication in Myeloma
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article appeared on Medscape.com.
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article appeared on Medscape.com.
Approval followed priority review and was based on efficacy and safety findings from the open-label PERSEUS trial involving 709 patients under age 70 years who were randomized to receive bortezomib, lenalidomide, and dexamethasone alone or in combination with daratumumab and hyaluronidase-fihj, according to the FDA.
Compared with bortezomib, lenalidomide, and dexamethasone alone, the addition of daratumumab and hyaluronidase-fihj resulted in a 60% reduction in the risk for disease progression or death (hazard ratio, 0.40). Median progression-free survival was not reached in either group.
Adverse reactions occurring in ≥ 20% of patients were peripheral neuropathy, fatigue, edema, pyrexia, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
The recommended dosage for this indication is 1800 mg daratumumab and 30,000 units hyaluronidase, according to the full prescribing information.
Daratumumab and hyaluronidase-fihj, which was first approved in 2020, has a range of other indications in multiple myeloma.
A version of this article appeared on Medscape.com.
FDA Calls AstraZeneca’s NSCLC Trial Design Into Question
The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone.
Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has.
However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points.
Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned.
When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery.
The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio.
AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.
One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment.
Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said.
To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.
The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.
However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so.
The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies.
FDA usually follows the advice of its advisory panels.
A version of this article appeared on Medscape.com.
The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone.
Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has.
However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points.
Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned.
When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery.
The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio.
AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.
One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment.
Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said.
To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.
The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.
However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so.
The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies.
FDA usually follows the advice of its advisory panels.
A version of this article appeared on Medscape.com.
The trial in question, AEGEAN, investigated perioperative durvalumab for resectable NSCLC tumors across 802 patients. Patients without EGFR or ALK mutations were randomly assigned to receive durvalumab before surgery alongside platinum-containing chemotherapy and after surgery for a year as monotherapy or to receive chemotherapy and surgery alone.
Patients receiving durvalumab demonstrated better event-free survival at 1 year (73.4% vs 64.5% without durvalumab) and a better pathologic complete response rate (17.2% vs 4.3% without). Currently, AstraZeneca is seeking to add the indication for durvalumab to those the agent already has.
However, at the July 25 ODAC meeting, the committee explained that the AEGEAN trial design makes it impossible to tell whether patients benefited from durvalumab before surgery, after it, or at both points.
Mounting evidence, including from AstraZeneca’s own studies, suggests that the benefit of immune checkpoint inhibitors, such as durvalumab, comes before surgery. That means prescribing durvalumab after surgery could be exposing patients to serious side effects and financial toxicity, with potentially no clinical benefit, “magnifying the risk of potential overtreatment,” the committee cautioned.
When AEGEAN was being designed in 2018, FDA requested that AstraZeneca address the uncertainty surrounding when to use durvalumab by including separate neoadjuvant and adjuvant arms, or at least an arm where patients were treated with neoadjuvant durvalumab alone to compare with treatment both before and after surgery.
The company didn’t follow through and, during the July 25 meeting, the committee wanted answers. “Why did you not comply with this?” asked ODAC committee acting chair Daniel Spratt, MD, a radiation oncologist at Case Western Reserve University in Cleveland, Ohio.
AstraZeneca personnel explained that doing so would have required many more subjects, made the trial more expensive, and added about 2 years to AEGEAN.
One speaker noted that the company, which makes more than $4 billion a year on durvalumab, would have taken about 2 days to recoup that added cost. Others wondered whether the motive was to sell durvalumab for as long as possible across a patient’s course of treatment.
Perhaps the biggest reason the company ignored the request is that “it wasn’t our understanding at that time that this was a barrier to approval,” an AstraZeneca regulatory affairs specialist said.
To this end, the agency asked its advisory panel to vote on whether it should require — instead of simply request, as it did with AstraZeneca — companies to prove that patients need immunotherapy both before and after surgery in resectable NSCLC.
The 11-member panel voted unanimously that it should make this a requirement, and several members said it should do so in other cancers as well.
However, when the agency asked whether durvalumab’s resectable NSCLC approval should be delayed until AstraZeneca conducts a trial to answer the neoadjuvant vs adjuvant question, the panel members didn’t think so.
The consensus was that because AEGEAN showed a decent benefit, patients and physicians should have it as an option, and approval shouldn’t be delayed. The panel said that the bigger question about the benefit of maintenance therapy should be left to future studies.
FDA usually follows the advice of its advisory panels.
A version of this article appeared on Medscape.com.
LBCL: CAR T Benefits Both Young and Old
“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
“This real-world study demonstrates that CD19 CAR-T cell therapy is feasible in a population of patients aged 75 years and older,” said senior author Pierre Bories, MD, PhD, of the Institute for Cancer Strasbourg-Europe, in Alsace, France. He presented the findings at the annual meeting of the European Hematology Association, held in Madrid, Spain.
Patients with R/R LBCL are often older, with many aged over 75, yet patients in those age groups are frequently underrepresented in clinical trials of CD19-directed CAR T-cell therapy, which has significantly improved outcomes for patients with R/R LBCL.
To further investigate differences in outcomes between older and younger patients with R/R LBCL treated with CAR-T cell therapy, Dr. Bories and colleagues conducted a retrospective analysis of 1,524 patients in the French DESCAR-T registry who were treated at treated at 31 centers in France and had at least two previous infusions of CAR-T cell therapy between April 2018 and September 2023.
Of the patients, 69.8% (n = 1065) were treated with axicabtagene ciloleucel (axi-cel), while 30.1% (n = 459) were treated with tisagenlecleucel (tisa-cel).
Among those patients, 125 were 75 years old or older, with a median age of 76, and the remaining 1399 were under the age of 75, with a median age of 62.
The two age groups had significant differences in terms of characteristics including gender, LBCL subset, number of prior lines of therapy, performance status, age-adjusted International Prognostic Index (IPI), rate of patients receiving a bridging therapy, response to the bridging therapy, and LDH at time of infusion.
Compared with patients aged 75 or younger, those who were 75 years or older had a higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) score, (31.2% high HCT-CI versus 16.8%, respectively; P < .001).
Patients over 75 also had fewer prior transplants than those under 75 (4.8% versus 21.8%, respectively; P < .001), and they more commonly received tisa-cel CAR-T cell therapy (43.2% versus 28.9%, respectively; P < .001).
Among 1457 patients with response data available, with a median follow-up of 12.7 months, there were no significant differences in terms of the best overall response rate (ORR) and complete response rates (CRR) between the two age groups, with rates of 74.8% for ORR and 62.6% for CRR among those 75 or older, compared with 78.0% and 60.8%, respectively, in the under 75 group (P = .425 and P = .699, respectively).
Likewise, the estimated median overall survival (OS) was 18.3 months in the 75 and older group and 24.0 months in the under 75 group (P = .12).
There were also no significant difference in terms of the estimated median progression-free survival, of 8.2 months in the 75 and older group versus 6.1 months in the under 75 group (P = .73).
In terms of safety, there were no significant differences in terms of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among patients 75 and older versus under 75, with 7.3% versus 7.4% developing CRS, respectively (P = .97), and 9.8% versus 12.4% developing ICANS (P = .39).
There were no significant differences between the age groups regarding ICU admissions, which occurred in about 24% of the cohorts, or the need for mechanical ventilation, which was necessary in about 3% of the entire cohort.
Of note, the overall rates of non-relapse mortality were more common in the 75 years and older group, among whom 19.5% of deaths were not related to lymphoma progression or relapse, compared with 8.1% in the under 75 group (P < .0001).
Early mortalities not related to relapse, defined as occurring before day 28 post-infusion, occurred among 3 patients aged 75 and older (2.4% of all patients 75 and older, representing 12.0% of all non-relapse mortality cases) compared with 16 patients under 75 (1.2% of those patients and 13.1% of all non-relapse mortality).
Infection was the main cause of non-relapse mortality in both groups, representing the cause in 57.7% of those under 75 and 54.2% of those aged 75 and older.
Patients 75 and older had a significantly higher risk of non-relapse mortality from infection (P = .0003), CRS (P = .022) or other causes, compared with those under 75 (P = .0004), but not from ICANS (P = .524).
“Our findings show a higher non-relapse mortality in this older population, which mainly relied on late infectious events, occurring after 28 days,” Dr. Bories said.
“There was also a higher rate of non-relapse mortality from infections, CRS or other causes in those 75 or older, but that did not translate to a lower overall survival in our patient sample,” he said.
Asked at the session about the implications of the higher infection risk in elderly patients, Dr. Bories said, “I think this deserves special attention and we have to be more careful with frail patients.
“This should obviously encourage the use of prophylaxis for a longer period of time.”
Dr. Bories noted that he and his team are currently conducting a more detailed propensity-matched comparison between axi-cel and tisa-cel in an older population.
The findings are consistent with those of other studies, among the latest including a 2024 real-world multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T cell therapy (mostly axi-cel).
That study showed comparable median progression-free and OS rates between those over and under the age of 70, however, in contrast to the current study, that study showed no significant differences in non-relapse mortality.
The ORR in that study also did not differ between age groups, exceeding 75%.
Of note, in that study, tisa‐cel treatment was associated with an approximately 60% higher risk of relapse and/or death compared with axi‐cel treatment, which the authors report was driven primarily by less favorable survival outcomes among tisa‐cel patients younger than age 70 years.
“In this context, some reports showed that axi‐cel may offer enhanced effectiveness compared to tisa‐cel in patients aged 65 and older, despite higher rates of neurotoxicity,” they wrote.
Nevertheless, the study’s overall findings indicate that “CAR T-cell therapy should be not withheld for elderly patients with r/r DLBCL,” the authors concluded.
Low CAR T Utilization in Elderly Patients
Overall, utilization of CAR-T cell therapy among older patients reportedly remains low, as demonstrated in one recent real-world study on the issue, involving 551 older patients with DLBCL.
The study showed that 19% of patients aged 65-69 and 22% of those aged 70-74 years received CAR-T cell therapy, compared with only 13% of those aged 75 and older.
“While CAR T-cell therapy in older patients is associated with favorable event-free survival comparable to outcomes in younger patients, CAR T-cell usage is low in older patients with DLBCL, which suggests an unmet need for more accessible, effective, and tolerable therapy,” reported first author Dia Chihara, MD, PhD, of the Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, in Houston, Texas, and colleagues.
Noting that “the use of current CAR-T cell therapy products seemed to be limited to selected patients,” the authors added that “this may change in the future with next-generation CAR T-cell therapy products.”
Dr. Bories disclosed relationships with Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, Janssen and the BMS foundation.
FROM EHA 2024
Doctor on Death Row: Ahmad Reza Djalali Begins Hunger Strike
Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.
Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.
He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.
In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
‘Spreading Corruption’
Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.
Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.
On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.
Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.
His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
‘Forgotten’ in Exchange
The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.
On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.
Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.
On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.
However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.
Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.
He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.
In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
‘Spreading Corruption’
Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.
Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.
On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.
Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.
His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
‘Forgotten’ in Exchange
The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.
On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.
Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.
On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.
However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Ahmad Reza Djalali, an Iranian-Swedish physician specializing in disaster medicine, has begun a hunger strike after being sentenced to death in 2017.
Last year, Iran set a grim record, leading the world in executions. The country carried out at least 853 executions, which accounted for three quarters of the officially recorded executions worldwide. The Iranian government uses the death penalty to intimidate political opponents, especially since the women’s uprising in 2022, and to exert pressure on Western states in diplomatic standoffs.
He emigrated to Sweden in 2009 and joined the Karolinska Institutet in Stockholm, Sweden. Over the years, he became one of Europe’s leading experts in disaster medicine. His work has been cited more than 700 times in medical literature, and he played a key role in establishing the emergency and disaster research center at the University of Piedmont.
In Italy, Denmark, and Sweden, Dr. Djalali helped hospitals and healthcare professionals in preparing for earthquakes, nuclear accidents, and terrorist attacks and designed several disaster medicine training programs.
‘Spreading Corruption’
Despite settling in Sweden with his family, Dr. Djalali never forgot his Iranian roots. His doctoral thesis was dedicated to the victims of the 2003 Bam earthquake in Iran, which killed 23,000 people. He expressed a desire to share his knowledge with his Iranian colleagues to help people. So when he was invited to participate in a 2016 conference at the University of Tehran, he accepted without hesitation.
Unfortunately, this decision had severe consequences. On April 25, 2016, as he was concluding his trip to Iran, the researcher was arrested by intelligence agents. After being held incommunicado for several days, he was officially accused of passing confidential information to Israeli intelligence services. According to his family, this accusation was baseless. They believed he was targeted for refusing to work for Iranian intelligence services in Europe.
On October 21, 2017, Dr. Djalali was sentenced to death for “spreading corruption on Earth,” a vague charge often used by Islamic courts against those who allegedly have challenged the regime. A few days later, a video of his “confessions” was broadcast on Iranian television. These confessions were coerced; Dr. Djalali later revealed that Iranian police had threatened to harm his mother in Iran and his family in Sweden.
Since then, Dr. Djalali and his loved ones have anxiously awaited the moment when the regime might carry out the sentence. Several times over the years, he has seemed on the verge of execution, only to receive a last-minute reprieve each time.
His imprisonment has taken a severe toll on his physical and mental health. He has reportedly lost 24 kg since his incarceration, and his family, who receive sporadic updates, suspect he has leukemia. Despite his deteriorating condition, the authorities have refused him access to a hematologist.
‘Forgotten’ in Exchange
The international medical community has rallied to secure Dr. Djalali’s release, but their efforts have so far been fruitless. The United Nations, the European Union, Amnesty International, several universities, and the World Medical Association have called for his release. In 2018, Sweden granted him citizenship in an attempt to increase pressure on Tehran, but Iranian law does not recognize dual citizenship.
On June 16, after nearly 7 years on death row, Dr. Djalali informed his family that he had begun a hunger strike. “It’s the only way to make my voice heard in the world,” he explained. “As a doctor, Ahmad Reza knows all too well that his fragile physical state makes a hunger strike potentially fatal, but he sees no other option. He suffers from cardiac arrhythmia, bradycardia, hypotension, chronic gastritis, anemia, and extreme weight loss following his two previous hunger strikes,” his wife told the press.
Aside from a potential (and unlikely) act of clemency by the Iranian authorities, Dr. Djalali’s best hope lies in a prisoner exchange. The Iranian government often imprisons foreign nationals to exchange them for Iranians detained in Western countries.
On June 15, Sweden agreed to release an Iranian dignitary serving a life sentence in exchange for the release of Swedish nationals detained in Iran. For a long time, Dr. Djalali’s family had hoped he would be included in this exchange.
However, to avoid jeopardizing the deal, the Swedish prime minister chose to accept the release of only two other Swedish nationals, leaving Dr. Djalali to his grim fate. “Mr Prime Minister, you have decided to abandon me at the enormous risk of being executed,” Dr. Djalali responded bitterly, knowing he could be hanged at any moment.
This story was translated from JIM using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.