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Autoantibodies could help predict cancer risk in scleroderma
TOPLINE:
METHODOLOGY:
- Included patients from the Johns Hopkins Scleroderma Center Research Registry and the University of Pittsburgh Scleroderma Center, Pittsburgh.
- A total of 676 patients with scleroderma and a history of cancer were compared with 687 control patients with scleroderma but without a history of cancer.
- Serum tested via line blot and enzyme-linked immunosorbent assay for an array of scleroderma autoantibodies.
- Examined association between autoantibodies and overall cancer risk.
TAKEAWAYS:
- Anti-POLR3 and monospecific anti-Ro52 were associated with significantly increased overall cancer risk.
- Anti-centromere and anti-U1RNP were associated with a decreased cancer risk.
- These associations remained when looking specifically at cancer-associated scleroderma.
- Patients positive for anti-Ro52 in combination with either anti-U1RNP or anti-Th/To had a decreased risk of cancer, compared with those who had anti-Ro52 alone.
IN PRACTICE:
This study is too preliminary to have practice application.
SOURCE:
Ji Soo Kim, PhD, of John Hopkins University, Baltimore, was the first author of the study, published in Arthritis & Rheumatology on July 24, 2023. Fellow Johns Hopkins researchers Livia Casciola-Rosen, PhD, and Ami A. Shah, MD, were joint senior authors.
DISCLOSURES:
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Donald B. and Dorothy L. Stabler Foundation, the Jerome L. Greene Foundation, the Chresanthe Staurulakis Memorial Discovery Fund, the Martha McCrory Professorship, and the Johns Hopkins inHealth initiative. The authors disclosed the following patents or patent applications: Autoimmune Antigens and Cancer, Materials and Methods for Assessing Cancer Risk and Treating Cancer.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Included patients from the Johns Hopkins Scleroderma Center Research Registry and the University of Pittsburgh Scleroderma Center, Pittsburgh.
- A total of 676 patients with scleroderma and a history of cancer were compared with 687 control patients with scleroderma but without a history of cancer.
- Serum tested via line blot and enzyme-linked immunosorbent assay for an array of scleroderma autoantibodies.
- Examined association between autoantibodies and overall cancer risk.
TAKEAWAYS:
- Anti-POLR3 and monospecific anti-Ro52 were associated with significantly increased overall cancer risk.
- Anti-centromere and anti-U1RNP were associated with a decreased cancer risk.
- These associations remained when looking specifically at cancer-associated scleroderma.
- Patients positive for anti-Ro52 in combination with either anti-U1RNP or anti-Th/To had a decreased risk of cancer, compared with those who had anti-Ro52 alone.
IN PRACTICE:
This study is too preliminary to have practice application.
SOURCE:
Ji Soo Kim, PhD, of John Hopkins University, Baltimore, was the first author of the study, published in Arthritis & Rheumatology on July 24, 2023. Fellow Johns Hopkins researchers Livia Casciola-Rosen, PhD, and Ami A. Shah, MD, were joint senior authors.
DISCLOSURES:
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Donald B. and Dorothy L. Stabler Foundation, the Jerome L. Greene Foundation, the Chresanthe Staurulakis Memorial Discovery Fund, the Martha McCrory Professorship, and the Johns Hopkins inHealth initiative. The authors disclosed the following patents or patent applications: Autoimmune Antigens and Cancer, Materials and Methods for Assessing Cancer Risk and Treating Cancer.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Included patients from the Johns Hopkins Scleroderma Center Research Registry and the University of Pittsburgh Scleroderma Center, Pittsburgh.
- A total of 676 patients with scleroderma and a history of cancer were compared with 687 control patients with scleroderma but without a history of cancer.
- Serum tested via line blot and enzyme-linked immunosorbent assay for an array of scleroderma autoantibodies.
- Examined association between autoantibodies and overall cancer risk.
TAKEAWAYS:
- Anti-POLR3 and monospecific anti-Ro52 were associated with significantly increased overall cancer risk.
- Anti-centromere and anti-U1RNP were associated with a decreased cancer risk.
- These associations remained when looking specifically at cancer-associated scleroderma.
- Patients positive for anti-Ro52 in combination with either anti-U1RNP or anti-Th/To had a decreased risk of cancer, compared with those who had anti-Ro52 alone.
IN PRACTICE:
This study is too preliminary to have practice application.
SOURCE:
Ji Soo Kim, PhD, of John Hopkins University, Baltimore, was the first author of the study, published in Arthritis & Rheumatology on July 24, 2023. Fellow Johns Hopkins researchers Livia Casciola-Rosen, PhD, and Ami A. Shah, MD, were joint senior authors.
DISCLOSURES:
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Donald B. and Dorothy L. Stabler Foundation, the Jerome L. Greene Foundation, the Chresanthe Staurulakis Memorial Discovery Fund, the Martha McCrory Professorship, and the Johns Hopkins inHealth initiative. The authors disclosed the following patents or patent applications: Autoimmune Antigens and Cancer, Materials and Methods for Assessing Cancer Risk and Treating Cancer.
A version of this article appeared on Medscape.com.
FROM ARTHRITIS & RHEUMATOLOGY
Neutropenia affects clinical presentation of pulmonary mucormycosis
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
, based on data from 114 individuals.
Diagnosis of pulmonary mucormycosis (PM), an invasive and potentially life-threatening fungal infection, is often delayed because of its variable presentation, wrote Anne Coste, MD, of La Cavale Blanche Hospital and Brest (France) University Hospital, and colleagues.
Improved diagnostic tools including molecular identification and image-guided lung biopsies are now available in many centers, but relations between underlying conditions, clinical presentations, and diagnostic methods have not been described, they said.
In a study published in the journal Chest, the researchers reviewed data from all cases of PM seen at six hospitals in France between 2008 and 2019. PM cases were based on European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Diabetes and trauma were included as additional host factors, and positive serum or tissue PCR (serum qPCR) were included as mycological evidence. Participants also underwent thoracic computed tomography (CT) scans.
The most common underlying conditions among the 114 patients were hematological malignancy (49%), allogeneic hematopoietic stem-cell transplantation (21%), and solid organ transplantation (17%).
Among the 40% of the cases that involved dissemination, the most common sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%).
A review of radiology findings showed consolidation in a majority of patients (58%), as well as pleural effusion (52%). Other findings included reversed halo sign (RHS, 26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%).
Bronchoalveolar lavage (BAL) was present in 46 of 96 patients (50%), and transthoracic lung biopsy was used for diagnosis in 8 of 11 (73%) patients with previous negative BALs.
Seventy patients had neutropenia. Overall, patients with neutropenia were significantly more likely than were those without neutropenia to show an angioinvasive presentation that included both RHS and disease dissemination (P < .05).
In addition, serum qPCR was positive in 42 of 53 patients for whom data were available (79%). Serum qPCR was significantly more likely to be positive in neutropenic patients (91% vs. 62%, P = .02). Positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01).
Possible reasons for the high rate of disseminated PM in the current study may be the large number of patients with pulmonary involvement, use of body CT data, and availability of autopsy results (for 11% of cases), the researchers wrote in their discussion.
Neutropenia and radiological findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in neutropenic patients and BAL examination in nonneutropenic patients. Lung biopsies are highly contributive in case of non-contributive BAL.
The findings were limited by several factors including the retrospective design, the inability to calculate sensitivity and specificity of diagnostic methods, and lack of data on patients with COVID-19, the researchers noted. However, the results provide real-life information for clinicians in centers with current mycological platforms, they concluded.
The study received no outside funding. Dr. Coste had no financial conflicts to disclose.
FROM THE JOURNAL CHEST
Long COVID disability court battles just ‘tip of iceberg’
At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.
But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.
“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”
As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.
“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”
The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.
Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.
But even in the courts, many encounter delays and hurdles to resolution.
In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.
His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”
Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.
Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.
He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.
Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.
“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”
Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.
Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.
Representatives of Reliance Standard didn’t respond to a request for comment.
The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.
Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.
“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”
Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.
For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.
Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.
Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.
All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.
“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”
Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.
Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.
“I have done letter upon letter of appeal to disability insurance companies,” she said.
Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.
“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.
“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”
A version of this article appeared on Medscape.com.
At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.
But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.
“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”
As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.
“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”
The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.
Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.
But even in the courts, many encounter delays and hurdles to resolution.
In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.
His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”
Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.
Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.
He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.
Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.
“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”
Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.
Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.
Representatives of Reliance Standard didn’t respond to a request for comment.
The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.
Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.
“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”
Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.
For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.
Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.
Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.
All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.
“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”
Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.
Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.
“I have done letter upon letter of appeal to disability insurance companies,” she said.
Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.
“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.
“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”
A version of this article appeared on Medscape.com.
At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.
But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.
“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”
As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.
“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”
The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.
Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.
But even in the courts, many encounter delays and hurdles to resolution.
In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.
His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”
Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.
Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.
He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.
Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.
“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”
Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.
Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.
Representatives of Reliance Standard didn’t respond to a request for comment.
The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.
Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.
“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”
Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.
For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.
Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.
Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.
All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.
“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”
Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.
Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.
“I have done letter upon letter of appeal to disability insurance companies,” she said.
Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.
“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.
“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”
A version of this article appeared on Medscape.com.
FDA approves quizartinib for newly diagnosed AML
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
On July 20 the FDA also approved the LeukoStrat CDx FLT3 Mutation Assay to determine whether patients have this mutation.
The agency granted quizartinib a first-line indication for use in combination with standard chemotherapy – cytarabine and anthracycline induction followed by cytarabine consolidation – and as maintenance monotherapy afterwards, in adults whose tumors express FLT3-ITD.
The FLT3 protein is a tyrosine kinase receptor found on hematopoietic stem cells. Wild-type FLT3 promotes cell survival, growth, and differentiation, but ITD (internal tandem duplication)-mutated FLT3, which quizartinib targets, is associated with a higher relapse risk and shorter survival. About a quarter of AML patients carry the mutation.
Approval was based on the phase 3 QuANTUM-First trial in over 500 patients with the mutation. Median overall survival among patients on standard chemotherapy randomly assigned to quizartinib was 31.9 months versus 15.1 months in patients randomly assigned to placebo, a 22.4% reduction in the risk of death (P = .0324).
Quizartinib is not indicated as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.
In a company press release, the drug’s manufacturer Daiichi Sankyo said quizartinib will be available in the United States soon.
Company executive Ken Takeshita, MD, called the approval “an important milestone, as patients with the FLT3-ITD subtype of AML can now be treated with the first-ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive.”
The FDA’s original decision date was April 24, but the agency pushed it back 3 months to review updates Daiichi Sankyo made to quizartinib’s Risk Evaluation and Mitigation Strategies (REMS) program in response to an agency request.
Quizartinib carries a boxed warning of QT prolongation, torsades de pointes, and cardiac arrest. Because of these risks, it’s only available through a new program, dubbed “Vanflyta REMS.”
In the trial, the most common adverse with quizartinib included lymphopenia (60%), hypokalemia (59%), hypoalbuminemia (53%), hypophosphatemia (52%), alkaline phosphatase increased (51%), hypomagnesemia (44%), febrile neutropenia (44%), diarrhea (42%), mucositis (38%), nausea (34%), and hypocalcemia (33%), among others.
The most common grade 3/4 adverse events were febrile neutropenia (43% with quizartinib vs. 41% with placebo), neutropenia (18% vs. 9%), hypokalemia (19% vs. 16%), and pneumonia (11% both). Adverse events were fatal in 11.3% of patients receiving quizartinib versus 9.7% of patients on placebo, mostly caused by infections.
In 2019, the FDA rejected quizartinib for FLT3-ITD mutated relapsed/refractory AML monotherapy in adults, after most of its oncology advisers thought the risk of treatment outweighed the benefits in an earlier trial.
A version of this article first appeared on Medscape.com.
ALL: Excess weight linked to much worse outcomes
The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.
“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.
ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.
Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”
The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.
Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.
In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”
As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).
Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).
In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.
As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).
Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”
The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.
In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.
Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.
Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.”
The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.
The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.
“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.
ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.
Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”
The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.
Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.
In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”
As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).
Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).
In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.
As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).
Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”
The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.
In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.
Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.
Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.”
The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.
The study, published in Blood Advances, doesn’t identify a culprit behind the worse outcomes in obese and overweight patients. However, it does highlight the limits of asparaginase-containing pediatric regimens in these patients, said study senior author and Dana-Farber Cancer Institute leukemia specialist Marlise R. Luskin, MD, in an interview.
“Pediatric-inspired regimens can be applied safely in adults up to the age of 50 years, with those of normal BMI having particularly good outcomes. Further research is needed to determine the best approach to treating patients of all ages with elevated BMIs,” Dr. Luskin said.
ALL is an uncommon cancer that kills about 1,390 people in the United States each year, according to the American Cancer Society. Most cases are in children, but most deaths are in adults, according to the ACS.
Research over the past 20 years has shown that younger adults “with ALL have better outcomes when they treated with intensive pediatric-style chemotherapy regimens than when they are treated with traditional adult regimens,” Dr. Luskin said. “Still, too many young adults do not have good outcomes. Either their disease is resistant to chemotherapy, or they experience significant side effects from treatment. Our main motivation for this study was to better understand which adolescents and younger adults have good outcomes with pediatric-style chemotherapy, and which patients require improved approaches.”
The researchers retrospectively tracked 388 patients aged 15-50 who were treated with Dana-Farber Consortium regimens from 2001 to 2021. A total of 46.7% were overweight or obese as defined by BMI. Of the rest, 2.6% were underweight, and 50.7% had normal weight. The study defined this combined group (53.3%) as having normal weight.
Most patients were male (61.9%), the median age was 24 years, and 35% were aged 30-50. All were treated with asparaginase-based regimens, although the components of the regimens changed over time.
In a bit of good news, “the study remarkably found equivalent overall survival among younger (aged 15-29) and older (aged 30-50) patients with normal BMI – 83% versus 85%, respectively [P = .89],” said lead author and Dana-Farber Cancer Institute advanced leukemia fellow Shai Shimony, MD. “This is an incredibly important finding as many are hesitant to offer pediatric regimens to patients over 30 years merely because of their age.”
As for differences by weight, both the normal and overweight/obese groups had identical rates of remission (87%; P = .84). However, overweight or obese patients had higher 4-year non-relapse mortality (11.7% vs. 2.8%; P = .006), worse event-free 4-year survival (63% vs. 77%; P = .003), and worse overall 4-year survival (64% vs. 83%; P = .0001).
Older obese/overweight patients (aged 30-50) were especially vulnerable to death, with worse overall 4-year survival versus their younger counterparts (55% vs. 73%; P = .023).
In another finding, the researchers also found that high triglyceride levels were common in patients, and this was linked to improved survival and decreased risk of relapse. These higher levels are likely linked to the drug regimen and “are not in and of themselves harmful or a reason to discontinue treatment,” Dr. Luskin said.
As for treatment-related side effects, an analysis of 353 patients found that grade III/IV hepatotoxicity – defined as elevation of AST, ALT, and/or bilirubin – was higher in patients who were overweight/obese versus normal weight (60.7% vs. 42.2%; P = .0005). Grade III/IV hyperglycemias were also higher in the overweight/obese group vs. normal weight (36.4% vs. 24.4%; P = .014).
Why might excess weight lead to worse outcomes? “We found that BMI was associated with more nonrelapse mortality, meaning death due to treatment-related side effects,” said Dr. Shimony. “This may be because patients with higher BMI are less able to tolerate chemotherapy, possibly due to more hyperglycemia, infection, and less overall resilience in the setting of complications. Obesity may also be associated with intrinsic disease resistance. This may be because adipose tissue protects lymphoblasts from the effects of chemotherapy or is due to underdosing of chemotherapy drugs.”
The study authors noted limitations to their research such as its reliance on BMI at diagnosis, without details about weight changes over time, and the lack of a systematic evaluation of measurable residual disease.
In an interview, Gwen Nichols, MD, chief medical officer of the Leukemia & Lymphoma Society, said it’s indeed possible that heavier patients may be underdosed with chemotherapy – especially older ones who may have more excess weight than children.
Dr. Nichols, who praised the study, highlighted another theory. “What causes you metabolically to be overweight may be connected to some reason to less metabolization of chemotherapy drugs,” she said.
Going forward, Dr. Shimony said “clinicians treating younger adults with ALL should monitor their patients with elevated BMI very closely for response and side effects. We recommend these patients be enrolled in clinical trials whenever possible so that more can be learned about how this group of patients responds to novel treatment approaches. Importantly, it is not yet known how obesity is associated with outcomes in nonasparaginase regimens such as hyper-CVAD or those approaches that rely on novel agents.”
The Foley Family Research Fund funded the study. Dr. Luskin disclosed research support from Abbvie and Novartis, and some other study authors reported various disclosures. Dr. Shimony and Dr. Nichols have no disclosures.
FROM BLOOD ADVANCES
Quizartinib boosts AML survival, regardless of SCT
The research shows that “FLT3 inhibitors are most effective in patients who are minimal residual disease (MRD) positive before allo-HCT,” first author Richard Schlenk, MD, of Heidelberg (Germany) University Hospital and the German Cancer Research Center, Heidelberg, said in an interview.
The findings are from a post-hoc analysis of the phase 3, multicenter QuANTUM-First trial, which involved patients with the FLT3-ITD mutation, who make up about a quarter of those with AML and who can have shorter survival and increased risk of relapse, compared with patients without the mutation. The current post-hoc analysis of the trial was presented at the European Hematology Association 2023 Congress.
The trial, published in April in The Lancet, showed significant benefits in newly diagnosed patients with FLT3-ITD AML who were treated with quizartinib and standard induction and consolidation therapy and then continued on quizartinib as monotherapy for up to 3 years.
In the trial, quizartinib, combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, was associated with a significant improvement in overall survival versus placebo (median 31.9 months versus 15.1 months, respectively; hazard ratio, 0.776; P = .0324).
For the post hoc analysis of the trial, the authors sought to evaluate if the effects were observed regardless of whether or not allo-HCT was received – which may not be recommended when patients go into remission after the first round of chemotherapy. The issue is important, as efficacy of other targeted therapy with the FLT3 inhibitors has been associated with allo-HCT treatment.
“Midostaurin, for example is mostly effective if [the drug] is followed by allo-HCT, and much less effective [no significant improvement] without allo-HCT,” Dr. Schlenk said.
The authors also sought to evaluate the relationship between minimal residual disease (MRD) prior to allo-HCT in FLT3-ITD and overall survival.
For the trial, 539 patients, with a median age of 56 were randomized to quizartinib (n = 268) or placebo (n = 271), and 147 patients (54.9%) in the quizartinib arm and 150 (55.4%) in the placebo arm achieved complete remission after induction. The rates of incomplete hematologic recovery (CRi) were 16.8% and 9.6%, respectively.
Of those achieving complete remission, 57.1% of patients on quizartinib and 48.7% of those receiving placebo underwent allo-HCT in the first complete remission. The median time to allo-HCT in the two groups was 3.5 months with quizartinib and 3.3 months for placebo.
Following the completion of allo-HCT, 61 patients (72.6%) receiving quizartinib and 36 (49.3%) receiving placebo started 3 years of continuation monotherapy.
In addition, 115 patients received allo-HCT outside of CR1, including 60 on quizartinib and 55 on placebo.
After adjustment for factors including region, age, and white blood count, patients treated with quizartinib treatment had a significantly higher overall survival (HR, 0.770; P = .0284), as did those receiving allo-HCT in CR1 (HR, 0.424; P < .0001).
Furthermore, patients receiving quizartinib had a longer overall survival regardless of whether they received allo-HCT in CR1 or not.
Of note, quizartinib-treated patients who were MRD positive prior to their allo-HCT transplant had a longer overall survival versus placebo (HR, 0.471); as did those who were MRD negative (HR, 0.717), to a lesser degree.
There were no new safety signals identified among patients undergoing allo-HCT.
Of note, cytomegalovirus infection was more common in the quizartinib group (11.8%) versus placebo (5.5%), while decreased appetite was less common with quizartinib (2.9%) versus placebo (12.1%).
Asked by an audience member about any risk of graft-versus-host disease (GVHD), Dr. Schlenk noted that “no difference between the quizartinib and placebo arms has been observed in GVHD acute and chronic.”
He added that patients “appear to benefit more from quizartinib if they have higher allelic frequency versus lower, overall,” and that younger patients, in general, showed greater benefit from quizartinib versus those over 60.
In general, “we see that for patients receiving allo-HCT transplantation, it’s beneficial to be randomized in the quizartinib arm [while] patients who did not undergo allo-HCT in first complete remission benefit equally when treated with quizartinib versus placebo,” he said in presenting the findings at the EHA meeting.
“And irrespective of pre–allo-HCT MRD status, longer survival was observed in those treated with quizartinib versus placebo, but most benefit was observed in those who were MRD positive.”
Quizartinib was approved in Japan this year in combination with chemotherapy for patients with newly diagnosed AML whose tumors harbor FLT3-ITD mutations.
The drug was granted a priority review by the U.S. Food and Drug Administration in October 2022. While the target action date was in April, a new decision date of July 21, 2023, is expected.
The study was sponsored by Daiichi Sankyo. Dr. Schlenk reported relationships with Daiichi Sankyo and other companies.
The research shows that “FLT3 inhibitors are most effective in patients who are minimal residual disease (MRD) positive before allo-HCT,” first author Richard Schlenk, MD, of Heidelberg (Germany) University Hospital and the German Cancer Research Center, Heidelberg, said in an interview.
The findings are from a post-hoc analysis of the phase 3, multicenter QuANTUM-First trial, which involved patients with the FLT3-ITD mutation, who make up about a quarter of those with AML and who can have shorter survival and increased risk of relapse, compared with patients without the mutation. The current post-hoc analysis of the trial was presented at the European Hematology Association 2023 Congress.
The trial, published in April in The Lancet, showed significant benefits in newly diagnosed patients with FLT3-ITD AML who were treated with quizartinib and standard induction and consolidation therapy and then continued on quizartinib as monotherapy for up to 3 years.
In the trial, quizartinib, combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, was associated with a significant improvement in overall survival versus placebo (median 31.9 months versus 15.1 months, respectively; hazard ratio, 0.776; P = .0324).
For the post hoc analysis of the trial, the authors sought to evaluate if the effects were observed regardless of whether or not allo-HCT was received – which may not be recommended when patients go into remission after the first round of chemotherapy. The issue is important, as efficacy of other targeted therapy with the FLT3 inhibitors has been associated with allo-HCT treatment.
“Midostaurin, for example is mostly effective if [the drug] is followed by allo-HCT, and much less effective [no significant improvement] without allo-HCT,” Dr. Schlenk said.
The authors also sought to evaluate the relationship between minimal residual disease (MRD) prior to allo-HCT in FLT3-ITD and overall survival.
For the trial, 539 patients, with a median age of 56 were randomized to quizartinib (n = 268) or placebo (n = 271), and 147 patients (54.9%) in the quizartinib arm and 150 (55.4%) in the placebo arm achieved complete remission after induction. The rates of incomplete hematologic recovery (CRi) were 16.8% and 9.6%, respectively.
Of those achieving complete remission, 57.1% of patients on quizartinib and 48.7% of those receiving placebo underwent allo-HCT in the first complete remission. The median time to allo-HCT in the two groups was 3.5 months with quizartinib and 3.3 months for placebo.
Following the completion of allo-HCT, 61 patients (72.6%) receiving quizartinib and 36 (49.3%) receiving placebo started 3 years of continuation monotherapy.
In addition, 115 patients received allo-HCT outside of CR1, including 60 on quizartinib and 55 on placebo.
After adjustment for factors including region, age, and white blood count, patients treated with quizartinib treatment had a significantly higher overall survival (HR, 0.770; P = .0284), as did those receiving allo-HCT in CR1 (HR, 0.424; P < .0001).
Furthermore, patients receiving quizartinib had a longer overall survival regardless of whether they received allo-HCT in CR1 or not.
Of note, quizartinib-treated patients who were MRD positive prior to their allo-HCT transplant had a longer overall survival versus placebo (HR, 0.471); as did those who were MRD negative (HR, 0.717), to a lesser degree.
There were no new safety signals identified among patients undergoing allo-HCT.
Of note, cytomegalovirus infection was more common in the quizartinib group (11.8%) versus placebo (5.5%), while decreased appetite was less common with quizartinib (2.9%) versus placebo (12.1%).
Asked by an audience member about any risk of graft-versus-host disease (GVHD), Dr. Schlenk noted that “no difference between the quizartinib and placebo arms has been observed in GVHD acute and chronic.”
He added that patients “appear to benefit more from quizartinib if they have higher allelic frequency versus lower, overall,” and that younger patients, in general, showed greater benefit from quizartinib versus those over 60.
In general, “we see that for patients receiving allo-HCT transplantation, it’s beneficial to be randomized in the quizartinib arm [while] patients who did not undergo allo-HCT in first complete remission benefit equally when treated with quizartinib versus placebo,” he said in presenting the findings at the EHA meeting.
“And irrespective of pre–allo-HCT MRD status, longer survival was observed in those treated with quizartinib versus placebo, but most benefit was observed in those who were MRD positive.”
Quizartinib was approved in Japan this year in combination with chemotherapy for patients with newly diagnosed AML whose tumors harbor FLT3-ITD mutations.
The drug was granted a priority review by the U.S. Food and Drug Administration in October 2022. While the target action date was in April, a new decision date of July 21, 2023, is expected.
The study was sponsored by Daiichi Sankyo. Dr. Schlenk reported relationships with Daiichi Sankyo and other companies.
The research shows that “FLT3 inhibitors are most effective in patients who are minimal residual disease (MRD) positive before allo-HCT,” first author Richard Schlenk, MD, of Heidelberg (Germany) University Hospital and the German Cancer Research Center, Heidelberg, said in an interview.
The findings are from a post-hoc analysis of the phase 3, multicenter QuANTUM-First trial, which involved patients with the FLT3-ITD mutation, who make up about a quarter of those with AML and who can have shorter survival and increased risk of relapse, compared with patients without the mutation. The current post-hoc analysis of the trial was presented at the European Hematology Association 2023 Congress.
The trial, published in April in The Lancet, showed significant benefits in newly diagnosed patients with FLT3-ITD AML who were treated with quizartinib and standard induction and consolidation therapy and then continued on quizartinib as monotherapy for up to 3 years.
In the trial, quizartinib, combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, was associated with a significant improvement in overall survival versus placebo (median 31.9 months versus 15.1 months, respectively; hazard ratio, 0.776; P = .0324).
For the post hoc analysis of the trial, the authors sought to evaluate if the effects were observed regardless of whether or not allo-HCT was received – which may not be recommended when patients go into remission after the first round of chemotherapy. The issue is important, as efficacy of other targeted therapy with the FLT3 inhibitors has been associated with allo-HCT treatment.
“Midostaurin, for example is mostly effective if [the drug] is followed by allo-HCT, and much less effective [no significant improvement] without allo-HCT,” Dr. Schlenk said.
The authors also sought to evaluate the relationship between minimal residual disease (MRD) prior to allo-HCT in FLT3-ITD and overall survival.
For the trial, 539 patients, with a median age of 56 were randomized to quizartinib (n = 268) or placebo (n = 271), and 147 patients (54.9%) in the quizartinib arm and 150 (55.4%) in the placebo arm achieved complete remission after induction. The rates of incomplete hematologic recovery (CRi) were 16.8% and 9.6%, respectively.
Of those achieving complete remission, 57.1% of patients on quizartinib and 48.7% of those receiving placebo underwent allo-HCT in the first complete remission. The median time to allo-HCT in the two groups was 3.5 months with quizartinib and 3.3 months for placebo.
Following the completion of allo-HCT, 61 patients (72.6%) receiving quizartinib and 36 (49.3%) receiving placebo started 3 years of continuation monotherapy.
In addition, 115 patients received allo-HCT outside of CR1, including 60 on quizartinib and 55 on placebo.
After adjustment for factors including region, age, and white blood count, patients treated with quizartinib treatment had a significantly higher overall survival (HR, 0.770; P = .0284), as did those receiving allo-HCT in CR1 (HR, 0.424; P < .0001).
Furthermore, patients receiving quizartinib had a longer overall survival regardless of whether they received allo-HCT in CR1 or not.
Of note, quizartinib-treated patients who were MRD positive prior to their allo-HCT transplant had a longer overall survival versus placebo (HR, 0.471); as did those who were MRD negative (HR, 0.717), to a lesser degree.
There were no new safety signals identified among patients undergoing allo-HCT.
Of note, cytomegalovirus infection was more common in the quizartinib group (11.8%) versus placebo (5.5%), while decreased appetite was less common with quizartinib (2.9%) versus placebo (12.1%).
Asked by an audience member about any risk of graft-versus-host disease (GVHD), Dr. Schlenk noted that “no difference between the quizartinib and placebo arms has been observed in GVHD acute and chronic.”
He added that patients “appear to benefit more from quizartinib if they have higher allelic frequency versus lower, overall,” and that younger patients, in general, showed greater benefit from quizartinib versus those over 60.
In general, “we see that for patients receiving allo-HCT transplantation, it’s beneficial to be randomized in the quizartinib arm [while] patients who did not undergo allo-HCT in first complete remission benefit equally when treated with quizartinib versus placebo,” he said in presenting the findings at the EHA meeting.
“And irrespective of pre–allo-HCT MRD status, longer survival was observed in those treated with quizartinib versus placebo, but most benefit was observed in those who were MRD positive.”
Quizartinib was approved in Japan this year in combination with chemotherapy for patients with newly diagnosed AML whose tumors harbor FLT3-ITD mutations.
The drug was granted a priority review by the U.S. Food and Drug Administration in October 2022. While the target action date was in April, a new decision date of July 21, 2023, is expected.
The study was sponsored by Daiichi Sankyo. Dr. Schlenk reported relationships with Daiichi Sankyo and other companies.
FROM THE EHA 2023 CONGRESS
SCD, beta-thalassemia: CRISPR-based gene therapy `transformative’
Results from the prespecified interim analyses of the phase 3 CLIMB THAL-111 and CLIMB SCD-121 studies, presented at the European Hematology Association annual congress, show that patients with beta-thalassemia who received exa-cel were able to remain transfusion-free for up to 40.7 consecutive months, while in patients with sickle cell disease, the treatment likewise provided up to 36.5 months of freedom from vaso-occlusive crises.
The findings underscore that “exa-cel can provide a one-time, functional cure to patients with beta-thalassemia and sickle cell disease,” said coauthor Franco Locatelli, MD, of Catholic University of the Sacred Heart, Bambino Gesù Children’s Hospital, Rome.
In a comment, senior investigator Haydar Frangoul, MD, noted that, “with almost 4 years of follow-up on patients with beta-thalassemia and sickle cell disease, it appears that the benefit is holding.”
“The engraftment of our edited cells appears very stable over time. There is no reason to believe it will change,” said Dr. Frangoul, who is medical director of pediatric hematology/oncology, Sarah Cannon Center for Blood Cancer at The Children’s Hospital at TriStar Centennial, Nashville, Tenn.
Burden is high; current curative options have caveats
Patients with transfusion-dependent beta-thalassemia may require blood transfusions as often as every 2-5 weeks because of genetic mutations causing the absence of functional hemoglobin and subsequent depletions in red blood cells. And with hemoglobin being an iron-rich protein, patients are also at risk of an iron accumulation in the body, adding the possible need for uncomfortable iron chelation therapy to prevent organ damage.
The measures are burdensome, but the need is dire. Life expectancy in beta-thalassemia without them is only about 5 years.
With SCD, patients can face severe pain from vaso-occlusive crises as sickled red blood cells block blood flow, potentially causing hospitalization and complications including kidney failure or stroke.
A cure does already exist for both genetic disorders in the form of allogeneic stem cell transplantation. However, that option requires a matched related stem cell donor, and fewer than 20% of patients have accessibility to such donors.
Gene therapy
Gene therapy offers a potentially ideal alternative, providing a possible “functional cure” without the need for a donor, by instead harvesting patients’ cells, fixing the mutation and transferring them back to the patient.
The Food and Drug Administration already approved a first gene therapy, betibeglogene autotemcel (beti-cel), for children and adults with transfusion dependent beta-thalassemia, in August 2022.
While beti-cel utilizes a viral vector to insert functional copies of a modified gene into patients’ extracted hematopoietic stem cells before transfusing them back, exa-cel instead uses CRISPR-CAS9 technology to edit the gene, allowing the body to produce fetal hemoglobin, in an approach believed to be more precise and efficient.
“As we explain to patients, it’s a difference between gene addition, which is what beti-cel is, or gene editing, which is what exa-cel is,” Dr. Frangoul explained.
Phase 3 trial interim results
In investigating exa-cel for beta-thalassemia, the ongoing CLIMB THAL-111 has enrolled 48 patients with a mean baseline age of 20, with 16 between the ages of 12 and 18. Of the patients, 28 (58.3%) had severe genotypes of disease.
Among 27 patients who were evaluable for the study endpoints of the current interim analysis, 24 (88.9%), achieved the primary endpoint of maintaining a weighted average hemoglobin of at least 9 g/dL without the need for a transfusion for at least 12 months (P < .0001).
Patients who achieved the transfusion independence for at least 12 months remained transfusion-free for a mean duration of 20.5 months, with a range of 12.1-40.7 months.
Of 3 patients who did not achieve the 12-month transfusion-free endpoint, substantial reductions in transfusion volume were nevertheless achieved, of 70.3%, 79.6%, and 95.5%, among the 3.
And for the CLIMB SCD-121 trial of SCD, 35 participants have been dosed with exa-cel; in the primary efficacy set of 17 patients, 16 of the 17 (94.1%) achieved the primary endpoint of having no severe vaso-occlusive crises for at least 12 months (P < .0001).
All patients, however, achieved the secondary endpoint of being free from in-patient hospitalizations for severe vaso-occlusive crises for at least 12 months (P < .0001).
Patients who achieved freedom from vaso-occlusive crises for at least 12 months remained free of the events for a mean of 18.7 months, ranging from 13.1 months to 36.5 months.
Durability, patient-reported outcomes favorable
Importantly, in both studies, hemoglobin levels, as well as levels of the edited BCL11A alleles in bone marrow CD34+ and peripheral blood nucleated cells, showed sustained stability over time, indicating durable editing of the cells, Dr. Locatelli said.
In terms of patient-reported quality-of-life, measures significantly improved during both trials at 24 months of follow-up, with significant improvements on the EuroQol visual analog scale, Functional Assessment of Cancer Therapy–General, and the Bone Marrow Transplantation Subscale.
Safety results were consistent with those observed with myeloablative busulfan-based conditioning regimen and autologous transplantation procedures, with adverse events that were manageable.
In the beta-thalassemia study, two patients experienced serious adverse events that were determined to be related to exa-cel, including one patient having symptoms in the context of hemophagocytic lymphohistiocytosis.
For the other patient, the serious adverse events consisted of delayed engraftment and thrombocytopenia, each also considered related to busulfan. None of the patients with SCD had serious adverse events related to exa-cel.
All serious adverse events were resolved, with no reports of deaths, study discontinuations, or malignancies.
Potentially first ever CRISPR-based FDA approval
While CRISPR-CAS9 gene editing is being investigated in multiple other trials in humans for various disorders, to date none have received FDA approval, which would make an approval for exa-cel a landmark development.
The therapy is currently under review, and Dr. Frangoul said the FDA has stated that a decision on the indication for SCD is expected by Dec. 8, 2023, and for beta-thalassemia, by March 2024.
Commenting on the research, Raffaella Colombatti, MD, a pediatric hematologist-oncologist and assistant professor of pediatrics at the University of Padova (Italy), underscored the need for a better curative alternative.
“Unfortunately, the other curative option, bone marrow transplant, is not available for all candidates due to the lack of suitable donors,” Dr. Colombatti said in an interview.
“And, although there are promising results from alternative donors and new conditioning regimens, a further option for selected patients with sickle cell disease and thalassemia utilizing gene therapy and gene editing is needed.”
Caveats regarding gene therapy for the two diseases that still need consideration include: “long-term safety results are still not available and eligibility criteria still needs to be explored outside clinical trials,” she said.
Furthermore, “costs and sustainability are also an issue,” Dr. Colombatti added.
The price of gene therapy is not cheap. With beti-cel priced at more than $2 million for the treatment, its manufacturer, Bluebird Bio, has reportedly already indicated that it will not pursue marketing in Europe because of unfavorable reimbursement policies, and a similar high price is anticipated for exa-cel.
Overall, however, the findings bode well for groundbreaking improvements in treatment of the two red blood cell disorders, Michael J. Eckrich, MD, MPH, medical director of pediatric stem cell transplant & cellular therapy at Atrium Health Levine Children’s Hospital Cancer and Blood Disorders in Charlotte, N.C., said in an interview.
“I do think that this is transformative therapy and will change our approach for patients with severe sickle cell disease in need of transplant,” said Dr. Eckrich, who has also been an investigator on the research of exa-cel for sickle cell disease.
“It might not be hard to imagine, that with the progress in gene therapies and gene editing, that allogeneic transplant will soon become obsolete for patients with sickle cell disease and beta-thalassemia.”
Dr. Locatelli is on the advisory board for Vertex Pharma and the speaker’s bureau for BluebirdBio. Dr. Frangoul and Dr. Colombatti are or have been consultants for Vertex Pharma.
Results from the prespecified interim analyses of the phase 3 CLIMB THAL-111 and CLIMB SCD-121 studies, presented at the European Hematology Association annual congress, show that patients with beta-thalassemia who received exa-cel were able to remain transfusion-free for up to 40.7 consecutive months, while in patients with sickle cell disease, the treatment likewise provided up to 36.5 months of freedom from vaso-occlusive crises.
The findings underscore that “exa-cel can provide a one-time, functional cure to patients with beta-thalassemia and sickle cell disease,” said coauthor Franco Locatelli, MD, of Catholic University of the Sacred Heart, Bambino Gesù Children’s Hospital, Rome.
In a comment, senior investigator Haydar Frangoul, MD, noted that, “with almost 4 years of follow-up on patients with beta-thalassemia and sickle cell disease, it appears that the benefit is holding.”
“The engraftment of our edited cells appears very stable over time. There is no reason to believe it will change,” said Dr. Frangoul, who is medical director of pediatric hematology/oncology, Sarah Cannon Center for Blood Cancer at The Children’s Hospital at TriStar Centennial, Nashville, Tenn.
Burden is high; current curative options have caveats
Patients with transfusion-dependent beta-thalassemia may require blood transfusions as often as every 2-5 weeks because of genetic mutations causing the absence of functional hemoglobin and subsequent depletions in red blood cells. And with hemoglobin being an iron-rich protein, patients are also at risk of an iron accumulation in the body, adding the possible need for uncomfortable iron chelation therapy to prevent organ damage.
The measures are burdensome, but the need is dire. Life expectancy in beta-thalassemia without them is only about 5 years.
With SCD, patients can face severe pain from vaso-occlusive crises as sickled red blood cells block blood flow, potentially causing hospitalization and complications including kidney failure or stroke.
A cure does already exist for both genetic disorders in the form of allogeneic stem cell transplantation. However, that option requires a matched related stem cell donor, and fewer than 20% of patients have accessibility to such donors.
Gene therapy
Gene therapy offers a potentially ideal alternative, providing a possible “functional cure” without the need for a donor, by instead harvesting patients’ cells, fixing the mutation and transferring them back to the patient.
The Food and Drug Administration already approved a first gene therapy, betibeglogene autotemcel (beti-cel), for children and adults with transfusion dependent beta-thalassemia, in August 2022.
While beti-cel utilizes a viral vector to insert functional copies of a modified gene into patients’ extracted hematopoietic stem cells before transfusing them back, exa-cel instead uses CRISPR-CAS9 technology to edit the gene, allowing the body to produce fetal hemoglobin, in an approach believed to be more precise and efficient.
“As we explain to patients, it’s a difference between gene addition, which is what beti-cel is, or gene editing, which is what exa-cel is,” Dr. Frangoul explained.
Phase 3 trial interim results
In investigating exa-cel for beta-thalassemia, the ongoing CLIMB THAL-111 has enrolled 48 patients with a mean baseline age of 20, with 16 between the ages of 12 and 18. Of the patients, 28 (58.3%) had severe genotypes of disease.
Among 27 patients who were evaluable for the study endpoints of the current interim analysis, 24 (88.9%), achieved the primary endpoint of maintaining a weighted average hemoglobin of at least 9 g/dL without the need for a transfusion for at least 12 months (P < .0001).
Patients who achieved the transfusion independence for at least 12 months remained transfusion-free for a mean duration of 20.5 months, with a range of 12.1-40.7 months.
Of 3 patients who did not achieve the 12-month transfusion-free endpoint, substantial reductions in transfusion volume were nevertheless achieved, of 70.3%, 79.6%, and 95.5%, among the 3.
And for the CLIMB SCD-121 trial of SCD, 35 participants have been dosed with exa-cel; in the primary efficacy set of 17 patients, 16 of the 17 (94.1%) achieved the primary endpoint of having no severe vaso-occlusive crises for at least 12 months (P < .0001).
All patients, however, achieved the secondary endpoint of being free from in-patient hospitalizations for severe vaso-occlusive crises for at least 12 months (P < .0001).
Patients who achieved freedom from vaso-occlusive crises for at least 12 months remained free of the events for a mean of 18.7 months, ranging from 13.1 months to 36.5 months.
Durability, patient-reported outcomes favorable
Importantly, in both studies, hemoglobin levels, as well as levels of the edited BCL11A alleles in bone marrow CD34+ and peripheral blood nucleated cells, showed sustained stability over time, indicating durable editing of the cells, Dr. Locatelli said.
In terms of patient-reported quality-of-life, measures significantly improved during both trials at 24 months of follow-up, with significant improvements on the EuroQol visual analog scale, Functional Assessment of Cancer Therapy–General, and the Bone Marrow Transplantation Subscale.
Safety results were consistent with those observed with myeloablative busulfan-based conditioning regimen and autologous transplantation procedures, with adverse events that were manageable.
In the beta-thalassemia study, two patients experienced serious adverse events that were determined to be related to exa-cel, including one patient having symptoms in the context of hemophagocytic lymphohistiocytosis.
For the other patient, the serious adverse events consisted of delayed engraftment and thrombocytopenia, each also considered related to busulfan. None of the patients with SCD had serious adverse events related to exa-cel.
All serious adverse events were resolved, with no reports of deaths, study discontinuations, or malignancies.
Potentially first ever CRISPR-based FDA approval
While CRISPR-CAS9 gene editing is being investigated in multiple other trials in humans for various disorders, to date none have received FDA approval, which would make an approval for exa-cel a landmark development.
The therapy is currently under review, and Dr. Frangoul said the FDA has stated that a decision on the indication for SCD is expected by Dec. 8, 2023, and for beta-thalassemia, by March 2024.
Commenting on the research, Raffaella Colombatti, MD, a pediatric hematologist-oncologist and assistant professor of pediatrics at the University of Padova (Italy), underscored the need for a better curative alternative.
“Unfortunately, the other curative option, bone marrow transplant, is not available for all candidates due to the lack of suitable donors,” Dr. Colombatti said in an interview.
“And, although there are promising results from alternative donors and new conditioning regimens, a further option for selected patients with sickle cell disease and thalassemia utilizing gene therapy and gene editing is needed.”
Caveats regarding gene therapy for the two diseases that still need consideration include: “long-term safety results are still not available and eligibility criteria still needs to be explored outside clinical trials,” she said.
Furthermore, “costs and sustainability are also an issue,” Dr. Colombatti added.
The price of gene therapy is not cheap. With beti-cel priced at more than $2 million for the treatment, its manufacturer, Bluebird Bio, has reportedly already indicated that it will not pursue marketing in Europe because of unfavorable reimbursement policies, and a similar high price is anticipated for exa-cel.
Overall, however, the findings bode well for groundbreaking improvements in treatment of the two red blood cell disorders, Michael J. Eckrich, MD, MPH, medical director of pediatric stem cell transplant & cellular therapy at Atrium Health Levine Children’s Hospital Cancer and Blood Disorders in Charlotte, N.C., said in an interview.
“I do think that this is transformative therapy and will change our approach for patients with severe sickle cell disease in need of transplant,” said Dr. Eckrich, who has also been an investigator on the research of exa-cel for sickle cell disease.
“It might not be hard to imagine, that with the progress in gene therapies and gene editing, that allogeneic transplant will soon become obsolete for patients with sickle cell disease and beta-thalassemia.”
Dr. Locatelli is on the advisory board for Vertex Pharma and the speaker’s bureau for BluebirdBio. Dr. Frangoul and Dr. Colombatti are or have been consultants for Vertex Pharma.
Results from the prespecified interim analyses of the phase 3 CLIMB THAL-111 and CLIMB SCD-121 studies, presented at the European Hematology Association annual congress, show that patients with beta-thalassemia who received exa-cel were able to remain transfusion-free for up to 40.7 consecutive months, while in patients with sickle cell disease, the treatment likewise provided up to 36.5 months of freedom from vaso-occlusive crises.
The findings underscore that “exa-cel can provide a one-time, functional cure to patients with beta-thalassemia and sickle cell disease,” said coauthor Franco Locatelli, MD, of Catholic University of the Sacred Heart, Bambino Gesù Children’s Hospital, Rome.
In a comment, senior investigator Haydar Frangoul, MD, noted that, “with almost 4 years of follow-up on patients with beta-thalassemia and sickle cell disease, it appears that the benefit is holding.”
“The engraftment of our edited cells appears very stable over time. There is no reason to believe it will change,” said Dr. Frangoul, who is medical director of pediatric hematology/oncology, Sarah Cannon Center for Blood Cancer at The Children’s Hospital at TriStar Centennial, Nashville, Tenn.
Burden is high; current curative options have caveats
Patients with transfusion-dependent beta-thalassemia may require blood transfusions as often as every 2-5 weeks because of genetic mutations causing the absence of functional hemoglobin and subsequent depletions in red blood cells. And with hemoglobin being an iron-rich protein, patients are also at risk of an iron accumulation in the body, adding the possible need for uncomfortable iron chelation therapy to prevent organ damage.
The measures are burdensome, but the need is dire. Life expectancy in beta-thalassemia without them is only about 5 years.
With SCD, patients can face severe pain from vaso-occlusive crises as sickled red blood cells block blood flow, potentially causing hospitalization and complications including kidney failure or stroke.
A cure does already exist for both genetic disorders in the form of allogeneic stem cell transplantation. However, that option requires a matched related stem cell donor, and fewer than 20% of patients have accessibility to such donors.
Gene therapy
Gene therapy offers a potentially ideal alternative, providing a possible “functional cure” without the need for a donor, by instead harvesting patients’ cells, fixing the mutation and transferring them back to the patient.
The Food and Drug Administration already approved a first gene therapy, betibeglogene autotemcel (beti-cel), for children and adults with transfusion dependent beta-thalassemia, in August 2022.
While beti-cel utilizes a viral vector to insert functional copies of a modified gene into patients’ extracted hematopoietic stem cells before transfusing them back, exa-cel instead uses CRISPR-CAS9 technology to edit the gene, allowing the body to produce fetal hemoglobin, in an approach believed to be more precise and efficient.
“As we explain to patients, it’s a difference between gene addition, which is what beti-cel is, or gene editing, which is what exa-cel is,” Dr. Frangoul explained.
Phase 3 trial interim results
In investigating exa-cel for beta-thalassemia, the ongoing CLIMB THAL-111 has enrolled 48 patients with a mean baseline age of 20, with 16 between the ages of 12 and 18. Of the patients, 28 (58.3%) had severe genotypes of disease.
Among 27 patients who were evaluable for the study endpoints of the current interim analysis, 24 (88.9%), achieved the primary endpoint of maintaining a weighted average hemoglobin of at least 9 g/dL without the need for a transfusion for at least 12 months (P < .0001).
Patients who achieved the transfusion independence for at least 12 months remained transfusion-free for a mean duration of 20.5 months, with a range of 12.1-40.7 months.
Of 3 patients who did not achieve the 12-month transfusion-free endpoint, substantial reductions in transfusion volume were nevertheless achieved, of 70.3%, 79.6%, and 95.5%, among the 3.
And for the CLIMB SCD-121 trial of SCD, 35 participants have been dosed with exa-cel; in the primary efficacy set of 17 patients, 16 of the 17 (94.1%) achieved the primary endpoint of having no severe vaso-occlusive crises for at least 12 months (P < .0001).
All patients, however, achieved the secondary endpoint of being free from in-patient hospitalizations for severe vaso-occlusive crises for at least 12 months (P < .0001).
Patients who achieved freedom from vaso-occlusive crises for at least 12 months remained free of the events for a mean of 18.7 months, ranging from 13.1 months to 36.5 months.
Durability, patient-reported outcomes favorable
Importantly, in both studies, hemoglobin levels, as well as levels of the edited BCL11A alleles in bone marrow CD34+ and peripheral blood nucleated cells, showed sustained stability over time, indicating durable editing of the cells, Dr. Locatelli said.
In terms of patient-reported quality-of-life, measures significantly improved during both trials at 24 months of follow-up, with significant improvements on the EuroQol visual analog scale, Functional Assessment of Cancer Therapy–General, and the Bone Marrow Transplantation Subscale.
Safety results were consistent with those observed with myeloablative busulfan-based conditioning regimen and autologous transplantation procedures, with adverse events that were manageable.
In the beta-thalassemia study, two patients experienced serious adverse events that were determined to be related to exa-cel, including one patient having symptoms in the context of hemophagocytic lymphohistiocytosis.
For the other patient, the serious adverse events consisted of delayed engraftment and thrombocytopenia, each also considered related to busulfan. None of the patients with SCD had serious adverse events related to exa-cel.
All serious adverse events were resolved, with no reports of deaths, study discontinuations, or malignancies.
Potentially first ever CRISPR-based FDA approval
While CRISPR-CAS9 gene editing is being investigated in multiple other trials in humans for various disorders, to date none have received FDA approval, which would make an approval for exa-cel a landmark development.
The therapy is currently under review, and Dr. Frangoul said the FDA has stated that a decision on the indication for SCD is expected by Dec. 8, 2023, and for beta-thalassemia, by March 2024.
Commenting on the research, Raffaella Colombatti, MD, a pediatric hematologist-oncologist and assistant professor of pediatrics at the University of Padova (Italy), underscored the need for a better curative alternative.
“Unfortunately, the other curative option, bone marrow transplant, is not available for all candidates due to the lack of suitable donors,” Dr. Colombatti said in an interview.
“And, although there are promising results from alternative donors and new conditioning regimens, a further option for selected patients with sickle cell disease and thalassemia utilizing gene therapy and gene editing is needed.”
Caveats regarding gene therapy for the two diseases that still need consideration include: “long-term safety results are still not available and eligibility criteria still needs to be explored outside clinical trials,” she said.
Furthermore, “costs and sustainability are also an issue,” Dr. Colombatti added.
The price of gene therapy is not cheap. With beti-cel priced at more than $2 million for the treatment, its manufacturer, Bluebird Bio, has reportedly already indicated that it will not pursue marketing in Europe because of unfavorable reimbursement policies, and a similar high price is anticipated for exa-cel.
Overall, however, the findings bode well for groundbreaking improvements in treatment of the two red blood cell disorders, Michael J. Eckrich, MD, MPH, medical director of pediatric stem cell transplant & cellular therapy at Atrium Health Levine Children’s Hospital Cancer and Blood Disorders in Charlotte, N.C., said in an interview.
“I do think that this is transformative therapy and will change our approach for patients with severe sickle cell disease in need of transplant,” said Dr. Eckrich, who has also been an investigator on the research of exa-cel for sickle cell disease.
“It might not be hard to imagine, that with the progress in gene therapies and gene editing, that allogeneic transplant will soon become obsolete for patients with sickle cell disease and beta-thalassemia.”
Dr. Locatelli is on the advisory board for Vertex Pharma and the speaker’s bureau for BluebirdBio. Dr. Frangoul and Dr. Colombatti are or have been consultants for Vertex Pharma.
FROM EHA 2023
Mental health questions cut from MD licensing applications in 21 states
Since May, physicians in 21 states are no longer being asked broad mental health or substance abuse questions when they apply for a medical license. That’s a major shift that could ease doctors’ concerns about seeking treatment, according to the Dr. Lorna Breen Heroes› Foundation, a physician burnout prevention group that tracks such changes.
The foundation was named in honor of Lorna Breen, MD, an emergency medicine physician in New York City who died by suicide in April 2020 as the pandemic unfolded. The rate of suicide among physicians is twice that of the general population.
“The issue is not whether a physician may have had a serious or a mild mental illness ... but whether they have any disabilities that may affect their current work,” said Peter Yellowlees, MD, distinguished professor of psychiatry at the University of California, Davis. “Asking about any past mental illness episodes, which may have occurred years previously ... is simply discriminatory and is an example of the stigma associated with mental disorders.”
The Breen Foundation has been working with state medical boards and hospitals to remove stigmatizing mental health and substance abuse questions from licensing and credentialing applications.
Dr. Breen had told her sister and brother-in-law shortly before her suicide that she was afraid she could lose her license and the career she loved if the medical board found out that she had received inpatient mental health treatment, said J. Corey Feist, JD, MBA, her brother-in-law and cofounder and president of the foundation.
She wasn’t aware that New York was a state that didn’t ask physicians questions about their mental health, said Mr. Feist.
“That’s why we want to make it very clear to physicians which states continue to ask these questions and which ones don’t,” Mr. Feist said.
Many physicians share Dr. Breen’s concern about professional consequences.
Four in 10 physicians said that they did not seek help for burnout or depression because they worried that their employer or state medical board would find out, according to the Medscape ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023.
One Oregon emergency department physician said that informing her state medical board about an episode of mania resulted in public disclosures, a 4-month long investigation, lost income, and poorer work evaluations. Looking back on her decision to be transparent with the board, Susan Haney, MD, said that she was naive. “The board is not your friend.”
Fearing for her career, now-retired ob.gyn. Robyn Alley-Hay, MD, never disclosed on licensing applications that in the 1990s, she had been hospitalized and treated for depression. She stopped practicing medicine in 2014 and now works as a life coach.
“I hated those questions because I felt I could never tell the whole truth,” Dr. Alley-Hay said. “But I could always truthfully answer ‘no’ to questions about impairment. That was a line that I wouldn’t cross – if you’re impaired, you shouldn’t be practicing.”
Does the focus on current impairment protect the public?
New York, Texas, California, Montana, Illinois, and North Carolina are among the 21 states that either ask no health-related questions or ask only a single question to address physical and mental health, said Mr. Feist.
Most of these changes align with the 2018 Federation of State Medical Boards recommendations, said Joe Knickrehm, FSMB vice president of communications. “Application questions must focus only on current impairment and not on illness, diagnosis, or previous treatment in order to be compliant with the Americans With Disabilities Act,” states the FSMB.
Mental health questions were often added to licensing and credentialing applications out of a “misplaced desire to protect patients and families from clinicians who might not be fit to give care. Yet there is no evidence they serve that function,” said Mr. Feist.
Marian Hollingsworth, a patient safety advocate in California, says medical boards have a responsibility to ensure that doctors pose no risk or a negligible risk to the public. She questioned whether the medical boards can adequately protect the public if they only ask about medical conditions rather than mental illness or substance abuse.
“There’s a fine line between privacy and right to know for public protection. I would want to see the approving medical board have assurance from a treating professional that this physician is stable and is doing well with continued treatment,” said Ms. Hollingsworth.
Legislation requires that mental health questions be removed
In March, Virginia became the first state to enact a law that requires all health care profession regulatory boards, including medical boards, to remove or replace mental health questions on licensing, certification, and registration applications.
The law requires that boards use the following wording if they replace mental health questions: “Do you have any reason to believe you would pose a risk to the safety or well-being of patients?” “Are you able to perform the essential functions of your job with or without reasonable accommodations?”
The Illinois General Assembly passed a more limited bill in May that requires medical boards to remove or replace mental health questions on its licensing applications. Gov. J. B. Pritzker (D) is expected to sign the bill.
The Virginia Healthcare and Hospital Association, which represents more than 100 hospitals and health systems in the state, partnered with the Medical Society of Virginia and the Virginia Nurses Association to advocate for the new legislation.
“The reason that the Virginia coalition pushed for the law was because the state’s medical boards weren’t acting quickly enough. Although state laws vary about what medical boards can do, legislation isn’t necessary in most states to change licensing questions,” said Mr. Feist.
Virginia hospitals began working last year with the foundation to change their mental health questions on credentialing applications. About 20% of Virginia’s hospitals have completed the process, including four large health systems: Inova, UVA Health, Centerra, and Children’s Hospitals of King’s Daughters, said Mr. Feist.
The foundation also challenged Lisa MacLean, MD, a psychiatrist and chief clinical wellness officer at the Henry Ford Medical Group in Detroit, to review their credentialing application for any stigmatizing mental health questions.
Dr. MacLean told the American Medical Association that she had found one question that needed to be changed but that it took time to get through the hospital›s approval process. Ultimately, the wording was changed from “a diagnosis or treatment of a physical, mental, chemical dependency or emotional condition” to “a diagnosis or treatment of any condition which could impair your ability to practice medicine.”
National medical organizations back changes
The Joint Commission, which accredits hospitals, has emphasized since 2020 that it doesn’t require hospitals to ask about an applicant’s mental health history.
“We strongly encourage organizations to not ask about past history of mental health conditions or treatment,” the Commission said in a statement. “It is critical that we ensure health care workers can feel free to access mental health resources.”
The Joint Commission said it supports the FSMB recommendations and the AMA’s recommendation that questions about clinicians’ mental health be limited to “conditions that currently impair the clinicians’ ability to perform their job.”
More than 40 professional medical organizations, including the American Academy of Family Physicians and the American Psychiatric Association, signed a joint statement in 2020 calling for changes in disclosure rules about mental health.
“The backing of major organizations is helpful because it’s changing the conversation that occurs within and outside the house of medicine,” said Mr. Feist.
Should doctors answer mental health questions?
Many states continue to ask questions about hospitalization and mental health diagnoses or treatment on their licensing and credentialing applications.
Yellowlees advises doctors to “be honest and not lie or deny past mental health problems, as medical boards tend to take a very serious view of physicians who do not tell the truth.”
However, the questions asked by medical boards can vary by state. “If it’s possible, physicians can give accurate but minimal information while trying to focus mainly on their current work capacity,” said Dr. Yellowlees.
He also suggested that physicians who are uncertain about how to respond to mental health questions consider obtaining advice from lawyers accustomed to working with the relevant medical boards.
Physicians who want to get involved in removing licensing and credentialing barriers to mental health care can find resources here and here.
A version of this article first appeared on Medscape.com.
Since May, physicians in 21 states are no longer being asked broad mental health or substance abuse questions when they apply for a medical license. That’s a major shift that could ease doctors’ concerns about seeking treatment, according to the Dr. Lorna Breen Heroes› Foundation, a physician burnout prevention group that tracks such changes.
The foundation was named in honor of Lorna Breen, MD, an emergency medicine physician in New York City who died by suicide in April 2020 as the pandemic unfolded. The rate of suicide among physicians is twice that of the general population.
“The issue is not whether a physician may have had a serious or a mild mental illness ... but whether they have any disabilities that may affect their current work,” said Peter Yellowlees, MD, distinguished professor of psychiatry at the University of California, Davis. “Asking about any past mental illness episodes, which may have occurred years previously ... is simply discriminatory and is an example of the stigma associated with mental disorders.”
The Breen Foundation has been working with state medical boards and hospitals to remove stigmatizing mental health and substance abuse questions from licensing and credentialing applications.
Dr. Breen had told her sister and brother-in-law shortly before her suicide that she was afraid she could lose her license and the career she loved if the medical board found out that she had received inpatient mental health treatment, said J. Corey Feist, JD, MBA, her brother-in-law and cofounder and president of the foundation.
She wasn’t aware that New York was a state that didn’t ask physicians questions about their mental health, said Mr. Feist.
“That’s why we want to make it very clear to physicians which states continue to ask these questions and which ones don’t,” Mr. Feist said.
Many physicians share Dr. Breen’s concern about professional consequences.
Four in 10 physicians said that they did not seek help for burnout or depression because they worried that their employer or state medical board would find out, according to the Medscape ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023.
One Oregon emergency department physician said that informing her state medical board about an episode of mania resulted in public disclosures, a 4-month long investigation, lost income, and poorer work evaluations. Looking back on her decision to be transparent with the board, Susan Haney, MD, said that she was naive. “The board is not your friend.”
Fearing for her career, now-retired ob.gyn. Robyn Alley-Hay, MD, never disclosed on licensing applications that in the 1990s, she had been hospitalized and treated for depression. She stopped practicing medicine in 2014 and now works as a life coach.
“I hated those questions because I felt I could never tell the whole truth,” Dr. Alley-Hay said. “But I could always truthfully answer ‘no’ to questions about impairment. That was a line that I wouldn’t cross – if you’re impaired, you shouldn’t be practicing.”
Does the focus on current impairment protect the public?
New York, Texas, California, Montana, Illinois, and North Carolina are among the 21 states that either ask no health-related questions or ask only a single question to address physical and mental health, said Mr. Feist.
Most of these changes align with the 2018 Federation of State Medical Boards recommendations, said Joe Knickrehm, FSMB vice president of communications. “Application questions must focus only on current impairment and not on illness, diagnosis, or previous treatment in order to be compliant with the Americans With Disabilities Act,” states the FSMB.
Mental health questions were often added to licensing and credentialing applications out of a “misplaced desire to protect patients and families from clinicians who might not be fit to give care. Yet there is no evidence they serve that function,” said Mr. Feist.
Marian Hollingsworth, a patient safety advocate in California, says medical boards have a responsibility to ensure that doctors pose no risk or a negligible risk to the public. She questioned whether the medical boards can adequately protect the public if they only ask about medical conditions rather than mental illness or substance abuse.
“There’s a fine line between privacy and right to know for public protection. I would want to see the approving medical board have assurance from a treating professional that this physician is stable and is doing well with continued treatment,” said Ms. Hollingsworth.
Legislation requires that mental health questions be removed
In March, Virginia became the first state to enact a law that requires all health care profession regulatory boards, including medical boards, to remove or replace mental health questions on licensing, certification, and registration applications.
The law requires that boards use the following wording if they replace mental health questions: “Do you have any reason to believe you would pose a risk to the safety or well-being of patients?” “Are you able to perform the essential functions of your job with or without reasonable accommodations?”
The Illinois General Assembly passed a more limited bill in May that requires medical boards to remove or replace mental health questions on its licensing applications. Gov. J. B. Pritzker (D) is expected to sign the bill.
The Virginia Healthcare and Hospital Association, which represents more than 100 hospitals and health systems in the state, partnered with the Medical Society of Virginia and the Virginia Nurses Association to advocate for the new legislation.
“The reason that the Virginia coalition pushed for the law was because the state’s medical boards weren’t acting quickly enough. Although state laws vary about what medical boards can do, legislation isn’t necessary in most states to change licensing questions,” said Mr. Feist.
Virginia hospitals began working last year with the foundation to change their mental health questions on credentialing applications. About 20% of Virginia’s hospitals have completed the process, including four large health systems: Inova, UVA Health, Centerra, and Children’s Hospitals of King’s Daughters, said Mr. Feist.
The foundation also challenged Lisa MacLean, MD, a psychiatrist and chief clinical wellness officer at the Henry Ford Medical Group in Detroit, to review their credentialing application for any stigmatizing mental health questions.
Dr. MacLean told the American Medical Association that she had found one question that needed to be changed but that it took time to get through the hospital›s approval process. Ultimately, the wording was changed from “a diagnosis or treatment of a physical, mental, chemical dependency or emotional condition” to “a diagnosis or treatment of any condition which could impair your ability to practice medicine.”
National medical organizations back changes
The Joint Commission, which accredits hospitals, has emphasized since 2020 that it doesn’t require hospitals to ask about an applicant’s mental health history.
“We strongly encourage organizations to not ask about past history of mental health conditions or treatment,” the Commission said in a statement. “It is critical that we ensure health care workers can feel free to access mental health resources.”
The Joint Commission said it supports the FSMB recommendations and the AMA’s recommendation that questions about clinicians’ mental health be limited to “conditions that currently impair the clinicians’ ability to perform their job.”
More than 40 professional medical organizations, including the American Academy of Family Physicians and the American Psychiatric Association, signed a joint statement in 2020 calling for changes in disclosure rules about mental health.
“The backing of major organizations is helpful because it’s changing the conversation that occurs within and outside the house of medicine,” said Mr. Feist.
Should doctors answer mental health questions?
Many states continue to ask questions about hospitalization and mental health diagnoses or treatment on their licensing and credentialing applications.
Yellowlees advises doctors to “be honest and not lie or deny past mental health problems, as medical boards tend to take a very serious view of physicians who do not tell the truth.”
However, the questions asked by medical boards can vary by state. “If it’s possible, physicians can give accurate but minimal information while trying to focus mainly on their current work capacity,” said Dr. Yellowlees.
He also suggested that physicians who are uncertain about how to respond to mental health questions consider obtaining advice from lawyers accustomed to working with the relevant medical boards.
Physicians who want to get involved in removing licensing and credentialing barriers to mental health care can find resources here and here.
A version of this article first appeared on Medscape.com.
Since May, physicians in 21 states are no longer being asked broad mental health or substance abuse questions when they apply for a medical license. That’s a major shift that could ease doctors’ concerns about seeking treatment, according to the Dr. Lorna Breen Heroes› Foundation, a physician burnout prevention group that tracks such changes.
The foundation was named in honor of Lorna Breen, MD, an emergency medicine physician in New York City who died by suicide in April 2020 as the pandemic unfolded. The rate of suicide among physicians is twice that of the general population.
“The issue is not whether a physician may have had a serious or a mild mental illness ... but whether they have any disabilities that may affect their current work,” said Peter Yellowlees, MD, distinguished professor of psychiatry at the University of California, Davis. “Asking about any past mental illness episodes, which may have occurred years previously ... is simply discriminatory and is an example of the stigma associated with mental disorders.”
The Breen Foundation has been working with state medical boards and hospitals to remove stigmatizing mental health and substance abuse questions from licensing and credentialing applications.
Dr. Breen had told her sister and brother-in-law shortly before her suicide that she was afraid she could lose her license and the career she loved if the medical board found out that she had received inpatient mental health treatment, said J. Corey Feist, JD, MBA, her brother-in-law and cofounder and president of the foundation.
She wasn’t aware that New York was a state that didn’t ask physicians questions about their mental health, said Mr. Feist.
“That’s why we want to make it very clear to physicians which states continue to ask these questions and which ones don’t,” Mr. Feist said.
Many physicians share Dr. Breen’s concern about professional consequences.
Four in 10 physicians said that they did not seek help for burnout or depression because they worried that their employer or state medical board would find out, according to the Medscape ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023.
One Oregon emergency department physician said that informing her state medical board about an episode of mania resulted in public disclosures, a 4-month long investigation, lost income, and poorer work evaluations. Looking back on her decision to be transparent with the board, Susan Haney, MD, said that she was naive. “The board is not your friend.”
Fearing for her career, now-retired ob.gyn. Robyn Alley-Hay, MD, never disclosed on licensing applications that in the 1990s, she had been hospitalized and treated for depression. She stopped practicing medicine in 2014 and now works as a life coach.
“I hated those questions because I felt I could never tell the whole truth,” Dr. Alley-Hay said. “But I could always truthfully answer ‘no’ to questions about impairment. That was a line that I wouldn’t cross – if you’re impaired, you shouldn’t be practicing.”
Does the focus on current impairment protect the public?
New York, Texas, California, Montana, Illinois, and North Carolina are among the 21 states that either ask no health-related questions or ask only a single question to address physical and mental health, said Mr. Feist.
Most of these changes align with the 2018 Federation of State Medical Boards recommendations, said Joe Knickrehm, FSMB vice president of communications. “Application questions must focus only on current impairment and not on illness, diagnosis, or previous treatment in order to be compliant with the Americans With Disabilities Act,” states the FSMB.
Mental health questions were often added to licensing and credentialing applications out of a “misplaced desire to protect patients and families from clinicians who might not be fit to give care. Yet there is no evidence they serve that function,” said Mr. Feist.
Marian Hollingsworth, a patient safety advocate in California, says medical boards have a responsibility to ensure that doctors pose no risk or a negligible risk to the public. She questioned whether the medical boards can adequately protect the public if they only ask about medical conditions rather than mental illness or substance abuse.
“There’s a fine line between privacy and right to know for public protection. I would want to see the approving medical board have assurance from a treating professional that this physician is stable and is doing well with continued treatment,” said Ms. Hollingsworth.
Legislation requires that mental health questions be removed
In March, Virginia became the first state to enact a law that requires all health care profession regulatory boards, including medical boards, to remove or replace mental health questions on licensing, certification, and registration applications.
The law requires that boards use the following wording if they replace mental health questions: “Do you have any reason to believe you would pose a risk to the safety or well-being of patients?” “Are you able to perform the essential functions of your job with or without reasonable accommodations?”
The Illinois General Assembly passed a more limited bill in May that requires medical boards to remove or replace mental health questions on its licensing applications. Gov. J. B. Pritzker (D) is expected to sign the bill.
The Virginia Healthcare and Hospital Association, which represents more than 100 hospitals and health systems in the state, partnered with the Medical Society of Virginia and the Virginia Nurses Association to advocate for the new legislation.
“The reason that the Virginia coalition pushed for the law was because the state’s medical boards weren’t acting quickly enough. Although state laws vary about what medical boards can do, legislation isn’t necessary in most states to change licensing questions,” said Mr. Feist.
Virginia hospitals began working last year with the foundation to change their mental health questions on credentialing applications. About 20% of Virginia’s hospitals have completed the process, including four large health systems: Inova, UVA Health, Centerra, and Children’s Hospitals of King’s Daughters, said Mr. Feist.
The foundation also challenged Lisa MacLean, MD, a psychiatrist and chief clinical wellness officer at the Henry Ford Medical Group in Detroit, to review their credentialing application for any stigmatizing mental health questions.
Dr. MacLean told the American Medical Association that she had found one question that needed to be changed but that it took time to get through the hospital›s approval process. Ultimately, the wording was changed from “a diagnosis or treatment of a physical, mental, chemical dependency or emotional condition” to “a diagnosis or treatment of any condition which could impair your ability to practice medicine.”
National medical organizations back changes
The Joint Commission, which accredits hospitals, has emphasized since 2020 that it doesn’t require hospitals to ask about an applicant’s mental health history.
“We strongly encourage organizations to not ask about past history of mental health conditions or treatment,” the Commission said in a statement. “It is critical that we ensure health care workers can feel free to access mental health resources.”
The Joint Commission said it supports the FSMB recommendations and the AMA’s recommendation that questions about clinicians’ mental health be limited to “conditions that currently impair the clinicians’ ability to perform their job.”
More than 40 professional medical organizations, including the American Academy of Family Physicians and the American Psychiatric Association, signed a joint statement in 2020 calling for changes in disclosure rules about mental health.
“The backing of major organizations is helpful because it’s changing the conversation that occurs within and outside the house of medicine,” said Mr. Feist.
Should doctors answer mental health questions?
Many states continue to ask questions about hospitalization and mental health diagnoses or treatment on their licensing and credentialing applications.
Yellowlees advises doctors to “be honest and not lie or deny past mental health problems, as medical boards tend to take a very serious view of physicians who do not tell the truth.”
However, the questions asked by medical boards can vary by state. “If it’s possible, physicians can give accurate but minimal information while trying to focus mainly on their current work capacity,” said Dr. Yellowlees.
He also suggested that physicians who are uncertain about how to respond to mental health questions consider obtaining advice from lawyers accustomed to working with the relevant medical boards.
Physicians who want to get involved in removing licensing and credentialing barriers to mental health care can find resources here and here.
A version of this article first appeared on Medscape.com.
AMA supports APRN oversight by both medical and nursing boards
In a move that raises the stakes in doctors’ ongoing scope-creep battle against nonphysician providers, the American Medical Association’s legislative body voted recently to change its policy on the supervision of advanced practice registered nurses (APRNs). AMA’s House of Delegates called for state medical boards to regulate APRNs in addition to nursing boards.
The AMA has long claimed that nonphysician providers, such as nurse practitioners (NPs) and physician assistants (PAs), need greater oversight because expanded scope of practice for advanced practice practitioners threatens patient safety and undermines the physician-led team model.
APRNs have been touted as a solution to expand access to care and reduce disparities, especially in rural and underserved communities, and they have been promoted by organizations such as the National Academy of Medicine. But the AMA disputes that scope expansions are necessary to increase access to care.
The organization that represents the nation’s physicians said in a prepared statement that it opposes scope expansions because removing doctors from the care team results in higher costs to the patient and lower quality care.
Several nursing organizations swiftly criticized the policy recommendation, including the American Nurses Association, the American Association of Nurse Practitioners, and the National Council of State Boards of Nursing.
The policy shift would create more administrative burdens for APRNs and generate “a downstream effect that only hurts patients,” particularly those in underserved communities without timely access to care, ANA president Jennifer Mensik Kennedy, PhD, MBA, RN, NEA-BC, told this news organization.
“The licensing and regulation of APRNs have never required the oversight of state medical boards,” she said, adding that it should remain the obligation of nursing regulatory bodies.
Jon Fanning, MS, CAE, CNED, chief executive officer of the AANP, called the AMA proposal “flawed.”
“The restrictive involvement of the board of medicine directly contributes to health care access challenges, resulting in continued low health care rankings, geographic disparities in care, and unnecessary regulatory cost in these states,” he said in a press release.
Still, the AMA has vowed to #StopScopeCreep. Securing stricter practice guidelines was a central theme of the association’s recent annual meeting and a goal of its plan to strengthen the physician workforce. The organization invests heavily in advocacy and education efforts to defeat state bills seeking to extend APRN authority. To that end, the AMA Scope of Practice Partnership, a coalition of over 100 medical associations, has awarded members $3.5 million in grants to combat scope-expansion legislation.
The AMA and the American College of Radiology recently partnered to create advocacy materials, including handouts encouraging patients to ask questions such as: “Will a physician be reviewing my chart, lab results, x-rays, and other tests?”
The policy recommendation comes as concerns mount over the potential for significant physician shortages, fueled partly by older physicians’ retirements and doctors reducing hours or exiting the workforce due to pandemic fatigue and burnout.
While practice regulations vary by state, a new federal bill could change that by broadening the authority of APRNs under Medicare and Medicaid guidelines. Introduced in the U.S. House of Representatives in April and supported by the ANA, the Improving Care and Access to Nurses Act would allow APRNs to perform more procedures, including cardiac and pulmonary rehabilitation and certification of terminal illness for hospice, according to an ANA press release.
In the meantime, several state legislatures are considering bills that would expand APRN scope of practice. Utah is the latest to join a growing list of states – about half now – offering full practice authority to NPs.
Other states offer a reduced scope of practice for APRNs, typically requiring a collaborative agreement with a supervising physician. The remaining states enforce tighter regulations and physician oversight.
A recent Medscape survey found that most physicians report having a good rapport with NPs but many have mixed feelings about giving them expanded practice roles, with one-third saying it would harm patient care. Feelings were only slightly more favorable toward PAs. However, about 75% of patients were either neutral or supportive of independent practice for NPs and PAs.
A version of this article first appeared on Medscape.com.
In a move that raises the stakes in doctors’ ongoing scope-creep battle against nonphysician providers, the American Medical Association’s legislative body voted recently to change its policy on the supervision of advanced practice registered nurses (APRNs). AMA’s House of Delegates called for state medical boards to regulate APRNs in addition to nursing boards.
The AMA has long claimed that nonphysician providers, such as nurse practitioners (NPs) and physician assistants (PAs), need greater oversight because expanded scope of practice for advanced practice practitioners threatens patient safety and undermines the physician-led team model.
APRNs have been touted as a solution to expand access to care and reduce disparities, especially in rural and underserved communities, and they have been promoted by organizations such as the National Academy of Medicine. But the AMA disputes that scope expansions are necessary to increase access to care.
The organization that represents the nation’s physicians said in a prepared statement that it opposes scope expansions because removing doctors from the care team results in higher costs to the patient and lower quality care.
Several nursing organizations swiftly criticized the policy recommendation, including the American Nurses Association, the American Association of Nurse Practitioners, and the National Council of State Boards of Nursing.
The policy shift would create more administrative burdens for APRNs and generate “a downstream effect that only hurts patients,” particularly those in underserved communities without timely access to care, ANA president Jennifer Mensik Kennedy, PhD, MBA, RN, NEA-BC, told this news organization.
“The licensing and regulation of APRNs have never required the oversight of state medical boards,” she said, adding that it should remain the obligation of nursing regulatory bodies.
Jon Fanning, MS, CAE, CNED, chief executive officer of the AANP, called the AMA proposal “flawed.”
“The restrictive involvement of the board of medicine directly contributes to health care access challenges, resulting in continued low health care rankings, geographic disparities in care, and unnecessary regulatory cost in these states,” he said in a press release.
Still, the AMA has vowed to #StopScopeCreep. Securing stricter practice guidelines was a central theme of the association’s recent annual meeting and a goal of its plan to strengthen the physician workforce. The organization invests heavily in advocacy and education efforts to defeat state bills seeking to extend APRN authority. To that end, the AMA Scope of Practice Partnership, a coalition of over 100 medical associations, has awarded members $3.5 million in grants to combat scope-expansion legislation.
The AMA and the American College of Radiology recently partnered to create advocacy materials, including handouts encouraging patients to ask questions such as: “Will a physician be reviewing my chart, lab results, x-rays, and other tests?”
The policy recommendation comes as concerns mount over the potential for significant physician shortages, fueled partly by older physicians’ retirements and doctors reducing hours or exiting the workforce due to pandemic fatigue and burnout.
While practice regulations vary by state, a new federal bill could change that by broadening the authority of APRNs under Medicare and Medicaid guidelines. Introduced in the U.S. House of Representatives in April and supported by the ANA, the Improving Care and Access to Nurses Act would allow APRNs to perform more procedures, including cardiac and pulmonary rehabilitation and certification of terminal illness for hospice, according to an ANA press release.
In the meantime, several state legislatures are considering bills that would expand APRN scope of practice. Utah is the latest to join a growing list of states – about half now – offering full practice authority to NPs.
Other states offer a reduced scope of practice for APRNs, typically requiring a collaborative agreement with a supervising physician. The remaining states enforce tighter regulations and physician oversight.
A recent Medscape survey found that most physicians report having a good rapport with NPs but many have mixed feelings about giving them expanded practice roles, with one-third saying it would harm patient care. Feelings were only slightly more favorable toward PAs. However, about 75% of patients were either neutral or supportive of independent practice for NPs and PAs.
A version of this article first appeared on Medscape.com.
In a move that raises the stakes in doctors’ ongoing scope-creep battle against nonphysician providers, the American Medical Association’s legislative body voted recently to change its policy on the supervision of advanced practice registered nurses (APRNs). AMA’s House of Delegates called for state medical boards to regulate APRNs in addition to nursing boards.
The AMA has long claimed that nonphysician providers, such as nurse practitioners (NPs) and physician assistants (PAs), need greater oversight because expanded scope of practice for advanced practice practitioners threatens patient safety and undermines the physician-led team model.
APRNs have been touted as a solution to expand access to care and reduce disparities, especially in rural and underserved communities, and they have been promoted by organizations such as the National Academy of Medicine. But the AMA disputes that scope expansions are necessary to increase access to care.
The organization that represents the nation’s physicians said in a prepared statement that it opposes scope expansions because removing doctors from the care team results in higher costs to the patient and lower quality care.
Several nursing organizations swiftly criticized the policy recommendation, including the American Nurses Association, the American Association of Nurse Practitioners, and the National Council of State Boards of Nursing.
The policy shift would create more administrative burdens for APRNs and generate “a downstream effect that only hurts patients,” particularly those in underserved communities without timely access to care, ANA president Jennifer Mensik Kennedy, PhD, MBA, RN, NEA-BC, told this news organization.
“The licensing and regulation of APRNs have never required the oversight of state medical boards,” she said, adding that it should remain the obligation of nursing regulatory bodies.
Jon Fanning, MS, CAE, CNED, chief executive officer of the AANP, called the AMA proposal “flawed.”
“The restrictive involvement of the board of medicine directly contributes to health care access challenges, resulting in continued low health care rankings, geographic disparities in care, and unnecessary regulatory cost in these states,” he said in a press release.
Still, the AMA has vowed to #StopScopeCreep. Securing stricter practice guidelines was a central theme of the association’s recent annual meeting and a goal of its plan to strengthen the physician workforce. The organization invests heavily in advocacy and education efforts to defeat state bills seeking to extend APRN authority. To that end, the AMA Scope of Practice Partnership, a coalition of over 100 medical associations, has awarded members $3.5 million in grants to combat scope-expansion legislation.
The AMA and the American College of Radiology recently partnered to create advocacy materials, including handouts encouraging patients to ask questions such as: “Will a physician be reviewing my chart, lab results, x-rays, and other tests?”
The policy recommendation comes as concerns mount over the potential for significant physician shortages, fueled partly by older physicians’ retirements and doctors reducing hours or exiting the workforce due to pandemic fatigue and burnout.
While practice regulations vary by state, a new federal bill could change that by broadening the authority of APRNs under Medicare and Medicaid guidelines. Introduced in the U.S. House of Representatives in April and supported by the ANA, the Improving Care and Access to Nurses Act would allow APRNs to perform more procedures, including cardiac and pulmonary rehabilitation and certification of terminal illness for hospice, according to an ANA press release.
In the meantime, several state legislatures are considering bills that would expand APRN scope of practice. Utah is the latest to join a growing list of states – about half now – offering full practice authority to NPs.
Other states offer a reduced scope of practice for APRNs, typically requiring a collaborative agreement with a supervising physician. The remaining states enforce tighter regulations and physician oversight.
A recent Medscape survey found that most physicians report having a good rapport with NPs but many have mixed feelings about giving them expanded practice roles, with one-third saying it would harm patient care. Feelings were only slightly more favorable toward PAs. However, about 75% of patients were either neutral or supportive of independent practice for NPs and PAs.
A version of this article first appeared on Medscape.com.
The ‘psychological warfare’ of prior authorization
Shikha Jain, MD, felt the urgency of the moment.
It was 10:00 AM. A young patient had stepped into her Chicago cancer clinic. His face was red, and he was struggling to breathe.
The man had primary mediastinal B-cell lymphoma, a rare, aggressive form of non-Hodgkin lymphoma. Many cases involve large, fast‐growing masses that expand into the lungs and compress respiratory pathways, sometimes leaving patients breathless.
Dr. Jain rushed to his side and walked him from the clinic to an ICU bed at the hospital nearby.
“He was so sick,” recalled Dr. Jain, currently a tenured associate professor of medicine in the division of hematology and oncology at the University of Illinois Cancer Center, Chicago. “He needed chemotherapy immediately.”
The standard chemotherapy regimen at the time – R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) – required prior authorization.
Dr. Jain’s patient did not have days to wait, so Dr. Jain requested an expedited approval. The insurance company responded quickly, denying the request for treatment.
That evening, after hours on the phone trying to reverse the denial, Dr. Jain was able to arrange a peer-to-peer conversation with the insurer. She explained her patient’s pressing need for chemotherapy: He would die if he continued to wait.
But Dr. Jain’s argument did not move the reviewer. At that point, she had reached her limit.
“I asked for the gentleman’s full name. I told him he would be responsible for this 30-year-old man’s death, and my next call would be to CNN,” Dr. Jain told this news organization. “And that is how I got my patient’s chemotherapy approved.”
Her patient received the regimen that evening. He later went into remission.
This incident occurred almost a decade ago, but it has stayed with Dr. Jain. She knows that her persistence in that moment meant the difference between her patient’s life and death.
There was the denial for standard-of-care staging and surveillance imaging – dotatate PET/CT – for her patient with neuroendocrine cancer. “The specific insurance company simply doesn’t approve this imaging, despite being around for years,” she said.
There was the patient with metastatic colon cancer who needed third-line therapy. His insurer took more than a month to reverse its denial for a recently approved drug, and in that time, the man’s disease progressed. “He eventually succumbed to the cancer after receiving the drug, but it’s unclear if his life was cut short by the delay in care,” Dr. Jain said.
And there is the maze of insurance company phone calls and transfers. On one call, Dr. Jain recalled being transferred six times before being connected to the right department to discuss approving standard-of-care chemotherapy for a patient. After being denied approval, Dr. Jain was put on hold to speak with a manager, and the call was abruptly disconnected.
“I have wasted so many hours on prior authorization and have seen months and months of patient care delays,” Dr. Jain said. “It’s easy to see why people just give up.”
For Dr. Jain, prior authorization has begun to “feel like psychological warfare,” she said. “To have everything questioned by people who don’t understand the basics of oncology is demoralizing.”
The growing administrative – and emotional – burden of prior authorization is contributing to physician burnout.
According to Medscape’s ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023, more than half of oncologists reported feeling burned out this year – the highest percentage in 5 years. When asked what factors led to burnout, most doctors surveyed pointed to an overabundance of bureaucratic tasks, and specifically, “insurance companies telling me how to practice medicine and controlling what the patients can and can’t do.”
“Burnout is a real problem in medicine,” said Kelly Anderson, PhD, MPP, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora. “While there are many factors that contribute to burnout, prior authorization is certainly one.”
In a 2022 survey from the American Medical Association, 88% of respondents reported that the burden associated with prior authorization requirements was “high or extremely high.”
Although insurers argue that prior authorization cuts down on unnecessary and expensive care, physicians in the AMA survey reported that this practice often leads to greater overall use of health care resources, including more emergency department and office visits.
“Insurers are confident that prior authorization is saving money overall, but there’s also no clear evidence of that,” Dr. Anderson noted. “Prior authorization may reduce spending without harming patients in some instances, but in others, it’s adding administrative burden, costs, and may be causing harm to patients.”
A version of this article originally appeared on Medscape.com.
Shikha Jain, MD, felt the urgency of the moment.
It was 10:00 AM. A young patient had stepped into her Chicago cancer clinic. His face was red, and he was struggling to breathe.
The man had primary mediastinal B-cell lymphoma, a rare, aggressive form of non-Hodgkin lymphoma. Many cases involve large, fast‐growing masses that expand into the lungs and compress respiratory pathways, sometimes leaving patients breathless.
Dr. Jain rushed to his side and walked him from the clinic to an ICU bed at the hospital nearby.
“He was so sick,” recalled Dr. Jain, currently a tenured associate professor of medicine in the division of hematology and oncology at the University of Illinois Cancer Center, Chicago. “He needed chemotherapy immediately.”
The standard chemotherapy regimen at the time – R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) – required prior authorization.
Dr. Jain’s patient did not have days to wait, so Dr. Jain requested an expedited approval. The insurance company responded quickly, denying the request for treatment.
That evening, after hours on the phone trying to reverse the denial, Dr. Jain was able to arrange a peer-to-peer conversation with the insurer. She explained her patient’s pressing need for chemotherapy: He would die if he continued to wait.
But Dr. Jain’s argument did not move the reviewer. At that point, she had reached her limit.
“I asked for the gentleman’s full name. I told him he would be responsible for this 30-year-old man’s death, and my next call would be to CNN,” Dr. Jain told this news organization. “And that is how I got my patient’s chemotherapy approved.”
Her patient received the regimen that evening. He later went into remission.
This incident occurred almost a decade ago, but it has stayed with Dr. Jain. She knows that her persistence in that moment meant the difference between her patient’s life and death.
There was the denial for standard-of-care staging and surveillance imaging – dotatate PET/CT – for her patient with neuroendocrine cancer. “The specific insurance company simply doesn’t approve this imaging, despite being around for years,” she said.
There was the patient with metastatic colon cancer who needed third-line therapy. His insurer took more than a month to reverse its denial for a recently approved drug, and in that time, the man’s disease progressed. “He eventually succumbed to the cancer after receiving the drug, but it’s unclear if his life was cut short by the delay in care,” Dr. Jain said.
And there is the maze of insurance company phone calls and transfers. On one call, Dr. Jain recalled being transferred six times before being connected to the right department to discuss approving standard-of-care chemotherapy for a patient. After being denied approval, Dr. Jain was put on hold to speak with a manager, and the call was abruptly disconnected.
“I have wasted so many hours on prior authorization and have seen months and months of patient care delays,” Dr. Jain said. “It’s easy to see why people just give up.”
For Dr. Jain, prior authorization has begun to “feel like psychological warfare,” she said. “To have everything questioned by people who don’t understand the basics of oncology is demoralizing.”
The growing administrative – and emotional – burden of prior authorization is contributing to physician burnout.
According to Medscape’s ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023, more than half of oncologists reported feeling burned out this year – the highest percentage in 5 years. When asked what factors led to burnout, most doctors surveyed pointed to an overabundance of bureaucratic tasks, and specifically, “insurance companies telling me how to practice medicine and controlling what the patients can and can’t do.”
“Burnout is a real problem in medicine,” said Kelly Anderson, PhD, MPP, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora. “While there are many factors that contribute to burnout, prior authorization is certainly one.”
In a 2022 survey from the American Medical Association, 88% of respondents reported that the burden associated with prior authorization requirements was “high or extremely high.”
Although insurers argue that prior authorization cuts down on unnecessary and expensive care, physicians in the AMA survey reported that this practice often leads to greater overall use of health care resources, including more emergency department and office visits.
“Insurers are confident that prior authorization is saving money overall, but there’s also no clear evidence of that,” Dr. Anderson noted. “Prior authorization may reduce spending without harming patients in some instances, but in others, it’s adding administrative burden, costs, and may be causing harm to patients.”
A version of this article originally appeared on Medscape.com.
Shikha Jain, MD, felt the urgency of the moment.
It was 10:00 AM. A young patient had stepped into her Chicago cancer clinic. His face was red, and he was struggling to breathe.
The man had primary mediastinal B-cell lymphoma, a rare, aggressive form of non-Hodgkin lymphoma. Many cases involve large, fast‐growing masses that expand into the lungs and compress respiratory pathways, sometimes leaving patients breathless.
Dr. Jain rushed to his side and walked him from the clinic to an ICU bed at the hospital nearby.
“He was so sick,” recalled Dr. Jain, currently a tenured associate professor of medicine in the division of hematology and oncology at the University of Illinois Cancer Center, Chicago. “He needed chemotherapy immediately.”
The standard chemotherapy regimen at the time – R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) – required prior authorization.
Dr. Jain’s patient did not have days to wait, so Dr. Jain requested an expedited approval. The insurance company responded quickly, denying the request for treatment.
That evening, after hours on the phone trying to reverse the denial, Dr. Jain was able to arrange a peer-to-peer conversation with the insurer. She explained her patient’s pressing need for chemotherapy: He would die if he continued to wait.
But Dr. Jain’s argument did not move the reviewer. At that point, she had reached her limit.
“I asked for the gentleman’s full name. I told him he would be responsible for this 30-year-old man’s death, and my next call would be to CNN,” Dr. Jain told this news organization. “And that is how I got my patient’s chemotherapy approved.”
Her patient received the regimen that evening. He later went into remission.
This incident occurred almost a decade ago, but it has stayed with Dr. Jain. She knows that her persistence in that moment meant the difference between her patient’s life and death.
There was the denial for standard-of-care staging and surveillance imaging – dotatate PET/CT – for her patient with neuroendocrine cancer. “The specific insurance company simply doesn’t approve this imaging, despite being around for years,” she said.
There was the patient with metastatic colon cancer who needed third-line therapy. His insurer took more than a month to reverse its denial for a recently approved drug, and in that time, the man’s disease progressed. “He eventually succumbed to the cancer after receiving the drug, but it’s unclear if his life was cut short by the delay in care,” Dr. Jain said.
And there is the maze of insurance company phone calls and transfers. On one call, Dr. Jain recalled being transferred six times before being connected to the right department to discuss approving standard-of-care chemotherapy for a patient. After being denied approval, Dr. Jain was put on hold to speak with a manager, and the call was abruptly disconnected.
“I have wasted so many hours on prior authorization and have seen months and months of patient care delays,” Dr. Jain said. “It’s easy to see why people just give up.”
For Dr. Jain, prior authorization has begun to “feel like psychological warfare,” she said. “To have everything questioned by people who don’t understand the basics of oncology is demoralizing.”
The growing administrative – and emotional – burden of prior authorization is contributing to physician burnout.
According to Medscape’s ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023, more than half of oncologists reported feeling burned out this year – the highest percentage in 5 years. When asked what factors led to burnout, most doctors surveyed pointed to an overabundance of bureaucratic tasks, and specifically, “insurance companies telling me how to practice medicine and controlling what the patients can and can’t do.”
“Burnout is a real problem in medicine,” said Kelly Anderson, PhD, MPP, assistant professor in the department of clinical pharmacy, University of Colorado at Denver, Aurora. “While there are many factors that contribute to burnout, prior authorization is certainly one.”
In a 2022 survey from the American Medical Association, 88% of respondents reported that the burden associated with prior authorization requirements was “high or extremely high.”
Although insurers argue that prior authorization cuts down on unnecessary and expensive care, physicians in the AMA survey reported that this practice often leads to greater overall use of health care resources, including more emergency department and office visits.
“Insurers are confident that prior authorization is saving money overall, but there’s also no clear evidence of that,” Dr. Anderson noted. “Prior authorization may reduce spending without harming patients in some instances, but in others, it’s adding administrative burden, costs, and may be causing harm to patients.”
A version of this article originally appeared on Medscape.com.