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84-year-old MD contests employer’s mandatory cognitive tests for older docs
Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.
Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.
According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.
Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.
The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.
The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.
The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.
There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.
Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.
It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.
However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.
“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.
In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”
Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”
However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”
Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.
What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.
One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”
Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.
So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”
Ms. Hoffman has no disclosures.
A version of this article first appeared on Medscape.com.
Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.
Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.
According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.
Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.
The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.
The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.
The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.
There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.
Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.
It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.
However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.
“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.
In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”
Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”
However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”
Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.
What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.
One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”
Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.
So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”
Ms. Hoffman has no disclosures.
A version of this article first appeared on Medscape.com.
Lylas G. Mogk, MD, recently sued Henry Ford Health and Henry Ford Medical Group in federal court, alleging that the mandatory cognitive test violates the Americans with Disabilities Act, the Age Discrimination in Employment Act, and two Michigan laws.
Dr. Mogk’s lawsuit follows a widely watched 2020 case in which the U.S. Equal Employment Opportunity Commission sued Yale New Haven Hospital, the teaching hospital of Yale University, for age discrimination. According to the lawsuit, the hospital illegally required neuropsychological and eye examinations of physicians aged 70 or older who sought to gain or renew staff privileges.
According to the lawsuit, Dr. Mogk is a member of Henry Ford Medical Group, which in 2017 required all members aged 70 and older to undergo cognitive screening tests. The tests would be repeated every 5 years thereafter, the lawsuit said, and anyone who refused would have to resign or be fired.
Dr. Mogk completed the screening, although no information about the results or outcome was mentioned in the lawsuit. It’s not clear whether Henry Ford’s cognitive test mandate remains in place; a spokesperson for Henry Ford Health and attorneys for Dr. Mogk declined to comment.
The number of practicing physicians in their 70s and beyond is rising. A 2021 report found that 12% of U.S. licensed physicians in 2020 were least 70 years old, up from 9% in 2010 and an increase from 75,627 to 120,510. The percentage of doctors aged 60-69 grew to 19% from 16% in 2010.
The number of health systems requiring testing of older physicians isn’t known, although various reports suggest at least a dozen have had mandates.
The University of California, San Diego, offers a physical and mental screening program that health organizations can use to evaluate “late-career physicians,” and a 2021 report noted that “Nebraska’s Children’s Hospital requires physicians aged 70 years and older to undergo an assessment by several peers, a complete physical, and unspecified cognitive screening.” Another system, Hartford HealthCare, mandated an annual reappointment process for clinicians aged 70 or older, requiring them to undergo various exams.
There’s evidence that physician performance declines with age. However, age-based cognitive testing can run afoul of federal and state laws against age discrimination, said Sharona Hoffman, JD, professor of law and bioethics at Case Western Reserve University, Cleveland, in an interview.
Federal law prohibits age-related restrictions on employment but allows exceptions in areas like public safety, said Ms. Hoffman, who’s written about age discrimination and testing requirements. Pilots, law enforcement officers, firefighters, and air controllers, for example, can be forced to retire at specific ages.
It’s not clear how many physicians took the cognitive tests required by Henry Ford Medical Group.
However, details are available about the policy at Yale New Haven Hospital: According to the EEOC lawsuit, from 2016 to 2019, 145 physicians aged 70 or older took the mandatory test. Of those, seven individuals failed either or both of the exams, 14 were listed as “borderline deficient,” and one was listed as “deficient.” Another five refused testing and either resigned or changed their status. The EEOC case against the hospital is still pending.
“You can make an argument that health care is like a public safety job because people put their lives in the hands of doctors,” Ms. Hoffman said.
In defending mandatory cognitive tests, she said, health care systems could say, “it’s not really discrimination; we’re not forcing them to retire, we’re not limiting their work in any way. We’re just doing testing to make sure they perform competently, and the ADA allows us to conduct testing that is job-related.”
Indeed, a Yale New Haven Hospital spokesman made an argument along these lines in a statement regarding the 2020 lawsuit: The “policy is designed to protect our patients from potential harm while including safeguards to ensure that our physicians are treated fairly. The policy is modeled on similar standards in other industries, and we are confident that no discrimination has occurred and will vigorously defend ourselves in this matter.”
However, Ms. Hoffman herself doesn’t buy these arguments. Requiring tests only for older physicians does appear to be discrimination based on age, she said. As an alternative, “employers can do close supervision of people. As soon as there are performance problems or patient complaints, you need to see a doctor or get testing done.”
Another option is to mandate tests at specific ages via licensing boards. “I don’t think that would be legally problematic,” Ms. Hoffman said.
What else can be done to protect patients from clinicians whose skills have significantly declined as they’ve aged? The 2021 report in Neurology Clinical Practice notes that there are disadvantages to several strategies.
One common approach, waiting to evaluate a clinician until an error occurs, can lead to patient harm, the report’s authors wrote. Relying on reporting by peers is problematic because “physicians have been very resistant to reporting colleagues who are impaired” and the “medical apprenticeship model discourages physicians from reporting on senior colleagues.”
Physician self-assessment is yet another option, but “loss of insight may be a component of an individual’s impairment,” the authors wrote.
So what’s the best solution? The authors recommended “a relatively brief cognitive screening followed by more extensive testing for the most impaired individuals.” This approach “appears most reliable in confidentially identifying truly impaired physicians while minimizing the chance of a falsely flagging unimpaired individuals. This strategy allows aging physicians to continue working while safeguarding both their reputations and their patients’ health.”
Ms. Hoffman has no disclosures.
A version of this article first appeared on Medscape.com.
PD-1 inhibitor improves outcomes in NHL subtype
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”
Genetic factors
Additional research presented in that ESMO session offered insights into the genetic factors that may play key roles in either response or resistance to anti-PD-1 therapy in peripheral T cell lymphoma (PTCL), of which extranodal NK/T cell lymphoma is a subtype.
The findings are from a genetic analysis of a phase 2 trial that demonstrated benefits the PD-1 inhibitor geptanolimab in patients with PTCL who failed initial chemotherapy.
Specifically, geptanolimab treatment was associated with an objective response rate of 40.4%, a complete response rate of 14.6%, and partial response rate of 25.8%.
Of 44 patients who had been treated with geptanolimab and had next-generation sequencing genetic data available, PD-L1 expression was found to be significantly elevated among those who had a complete or partial response, whereas PD-L1 expression was lower among those who had disease progression, which is consistent with previous research suggesting that low PD-L1 expression is linked to poorer response to anti-PD-1 therapies.
Tumor mutation burden did not exhibit significant prognostic value. However, the authors noted that this may be confounded by variation across PTCL subtypes.
Among other key findings were that JAK3 and EZH2 mutations, which are among the top genes frequently mutated in PTCL and extranodal NK/T cell lymphoma, were consistently associated with low PD-L1 expression (P < .05) and shorter progression-free survival (HR 5.97; P = .027, JAK3, and HR 4.76; P = .027 EZH2).
“Notably, we found JAK3 mutations, which are vital and prevalent in PTCL, reduced PD-L1 levels in vivo and in vitro, which are of great clinical and biological sense,” said the study’s first author, Ning Lou, MD, of the Cancer Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, in Beijing.
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand in Dijon, France, said that the findings are especially notable in relation to extranodal NK/T cell lymphoma.
“The clinical relevance of anti PD1 is mainly observed in relapsing/recurrent extranodal NK/T cell lymphoma, and much less in other T-cell lymphoma subtypes,” he told this news organization.
“So identifying molecular events associated with the chance of response to a PD1 blocker in relapsing extranodal NK/T cell lymphoma is important as PD1-blockers are recommended to treat [those] patients,” Dr. Casasnovas added.
Furthermore, “the interest of next-generation sequencing to identify JAK3 mutations associated with low level of PDL1 expression and weak response to anti PD1 blockers is important as JAK3 mutated tumors are potentially targetable by JAK inhibitors such as tofacitinib,” he said.
“Obviously this assumption has to be tested in clinical trials but it’s an interesting lead.”
The research on toripalimab additionally shows that “the combination of radiotherapy and PD1 blockers provides a high response rate in patients who are nonresponders to asparaginase-based chemotherapy on the basis of PET evaluation and could be a new option for optimizing the first line treatment of extranodal NK/T cell lymphoma patients,” Dr. Casasnovas added.
The authors and Dr. Casasnovas had no disclosures to report.
FROM ESMO 2023
Rare lymphomas: Desperately seeking new txs
“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.
Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.
One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.
“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”
There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.
Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.
Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”
Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.
Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.
One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.
“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”
There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.
Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.
Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”
Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
“Over the past 5 years, researchers have gotten a clearer picture of the different subtypes of peripheral T-cell lymphomas, and with this knowledge we are trying to identify potential targets of new treatments. Despite some progress, the need for these new treatments is still acute, due to the disease’s many subtypes and the difficulty of enrolling sufficient numbers of patients in clinical trials,” said Julie M. Vose, MD, MBA, of the University of Nebraska Medical Center, Omaha, speaking at the Lymphoma, Leukemia and Myeloma Congress 2023, in New York. Before her presentation at this year’s conference, Dr. Vose was awarded the SASS-ARENA Foundation’s John Ultmann Award for Major Contributions to Lymphoma Research.
Dr. Vose noted that only one subtype of PTCL, ALK+ ALCL, responds well to frontline treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone). Patients with the ALK+ ALCL signature treated with CHOP have a 5-year overall survival (OS) rate of 70%-90%, but this group only makes up about 6% of PTCL cases in North America, she added.
One of the most promising breakthroughs in treatment has been the addition of the anti-CD30 antibody-drug conjugate brentuximab vedotin (BV) to chemotherapy with CHP (cyclophosphamide, doxorubicin, prednisone), Dr. Vose said. Results from the ECHELON-2 trial indicate that CD30+ PTCL patients have improved performance with R-CHP, compared with CHOP; 5-year progression free survival (PFS) rates were 51.4% with R+CHP versus 43.0% with CHOP, and 5-year overall survival rates were 70.1% versus 61.0%, respectively.
“ALCL is one of the most prevalent PTCL subtypes and accounts for about 24% of all PTCL; the current standard-of-care for induction treatment in these patients is BV-CHP,” said Jia Ruan, MD, PhD, of Weill Cornell Medicine in New York. Dr. Ruan explained the limitation of adding BV-CHP, saying “We don’t have as effective biological targeted therapies in other subtypes of T-cell lymphoma, such as PTCL NOS [not-other specified] or angioimmunoblastic T-cell lymphoma.”
There is evidence that autologous stem cell transplant (ACST) can increase PFS and OS in newly diagnosed patients with angioimmunoblastic T-cell lymphoma (AITL), but not in patients with other types of newly diagnosed PTCL. The estimated 2-year OS and PFS for patients with AITL who received ASCT + chemotherapy were 93.3% and 68.8 respectively versus 52.9% and 41.2 in the non-ASCT group. This news is promising, yet Dr. Vose presented statistics indicating that AITL PTCL has been estimated to account for less than 19% of PTCL cases.
Despite the improvements in PFS and OS in a few subtypes for frontline PTCL, 60% of patients with non-ALCL PTCL will relapse, and relapsed/ refractory (R/R) PTCL patients have a median PFS of 9.6 months. Several studies have shown some promise for improving outcomes in R/R PTCL patients, such as the phase-II PRIMO study of duvelisib (a dual PI3K-delta,gamma inhibitor), in which there was an overall response rate of 50% and a complete response rate of 32%. Despite these modest gains, the prognosis for most PTCL patients remains poor. Dr. Vose concluded her presentation by reiterating the need for new agents and for further research. She emphasized that studies will need to be collaborative and international to enroll sufficient patients.
Dr Ruan drew a similar conclusion, noting “We need to increase clinical, translational and basic research on a collaborative scale, so that we can advance bench-to-bedside discovery and bring new treatment to patients quickly.”
Dr. Vose disclosed research funding from Epizyme, GenMab, Kite, Novartis, and Lilly. Dr. Ruan disclosed clinical research trial support from BMS and Daiichi Sankyo.
AT LLM CONGRESS 2023
Ocular MALT lymphoma: Radiation reduces relapse
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
“Our study represents the largest institutional cohort analysis on the course of patients with stage I POAML,” said first author Linrui Gao, MD, of the department of radiation oncology at the National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, in Beijing.
Dr. Gao presented these findings at ESMO 2023, held in Madrid.
“We confirm the indolent nature of this stage I disease, with mortality that is similar to the general population and a low rate of lymphoma-attributed mortality,” she said, adding that “radiation therapy was associated with the lowest relapse or disease progression, compared with [other treatments].”
POAML, which can involve lesions in areas including the eyelid, conjunctiva, orbit, and lacrimal gland, makes up about 7% of mucosa-associated lymphoid tissue (MALT) lymphomas. However, the incidence is reported to be steadily increasing. With the majority of patients, 70%-85%, diagnosed as stage I, consensus on treatment approaches is lacking.
Guidelines typically recommend radiation therapy as the standard of care, and approximately 70% of POAML patients do receive the therapy, compared with only about 36% of those with early-stage MALT lymphoma, with the indolent nature of the disease likely weighing on decisions to forgo the treatment, Dr. Gao reported.
“Adoption of initial radiotherapy in early-stage POAML is relatively low worldwide, with possible reasons being [concerns] of a low survival benefit and long-term toxicities,” she said.
To evaluate the long-term outcomes based on baseline clinical features and treatments, Dr. Gao and colleagues conducted a retrospective study of 262 patients with stage I POAML (ipsilateral or bilateral disease), enrolled between January 2000 and December 2020 at two hospitals in China.
Of the patients, who had a median age of 55 and a male-female ratio of 1:3, 82 were initially treated with radiation therapy, 81 with observation, 70 with surgery, and 29 with systemic treatment.
Those receiving radiation therapy had higher rates of an Eastern Cooperative Oncology Group performance status of 1 or higher (P = .02), higher elevations of LDH (P = .03), and higher rates of chronic disease (P < .001), while other baseline characteristics between the groups, including age, T stage, symptom duration, and other factors, were similar.
With a median follow-up of 66 months, the 5-year and 10-year overall survival rates were 96.8% and 90%, respectively, which is similar to the survival rate in the general population in China.
Likewise, the 5- and 10-year rates of lymphoma-specific mortality were both extremely low, at 0.4%, and the corresponding rates of competing nonlymphoma mortality at 5 and 10 years were 2.3% and 4.2%, also consistent with the general population.
The 5- and 10-year mortality rates remained similar to the general population in stratifying patients according to the initial treatment type (P = .767 between treatments).
In terms of recurrence, the overall failure rates were relatively high, with 19.5% of patients experiencing relapse at 5 years and 24.05% at 10 years.
“The failure rates show that the risk of relapse in POAML does not decrease over time,” Dr. Gao said.
Notably, those treated with radiation therapy had a significantly decreased 5-year cumulative risk of failure (8.5%), compared with those who only received observation (29.6%), surgery (22.9%), or systemic treatment (17.2%; overall, P = .002).
The most common failure site was the ipsilateral orbit, and again, rates of those relapses were significantly lower with radiation therapy (2.4%), compared with observation (23.5%), surgery (21.4%), and systemic treatment (17.3%).
However, rates of relapses in other sites, including the contralateral orbit, extraocular site, and multiple sites, were similar among all treatment groups. One patient receiving systemic treatment had large cell transformation, associated with poorer outcomes.
Strategies after recurrence were salvage therapy for 53 patients, including 27 receiving radiation therapy, and observation for 10 patients.
Dr. Gao noted that treatment failure was not associated with higher mortality rates. “However, given the limited number of cases, we think more cases and longer follow-up are needed,” she told MDedge.
Among the most common acute toxicities were ocular dermatitis or mucositis, described as mild, among 23 patients receiving radiation therapy. Nine patients experienced postoperative complications of mild eye irritation and periorbital edema, and five patients receiving systemic treatment experienced grade 2-3 leukopenia. There were no severe adverse events.
In terms of late ocular adverse effects, overall, 3 patients in the radiation therapy group developed cataracts and 143 patients developed dry-eye disease.
“Radiation therapy was associated with the lowest rate of relapse progression, compared with observation, surgery, and systemic treatment, with similar overall and recurrent survival,” Dr. Gao said.
“Based on our study results, radiotherapy should be considered as the optimal treatment for all patients with stage I disease because of its lowest failure risk and minor toxicity,” Dr. Gao told MDedge.
“However, the radiotherapy dose and techniques should be further optimized in good clinical trials,” she noted. “There are some clinical studies undergoing to explore the modern radiotherapy strategy, including by our group.”
Commenting on the study, discussant Olivier Casasnovas, MD, PhD, of the department of hematology, University Hospital Francois Mitterrand, in Dijon, France, noted that “interestingly, radiotherapy reduced the risk of local relapse but not systemic relapse.”
Benefits linked to radiation therapy dose?
Furthermore, the study adds to evidence suggesting the role of dose in radiation therapy’s benefits in POAML, Dr. Casanovas noted. He pointed to previous research showing that, with a median radiotherapy dose of 26 Gy, stage I POAML patients had a local relapse rate of 9.5%, whereas in the current study, which reported a median radiotherapy dose of 30.6 Gy, the local relapse rate was just 2%.
“Regarding the risk of local relapse, it’s important to see that, as previous published, the risk of a local relapse depends probably on the dose of radiotherapy,” he said.
The results indicate that “radiation therapy could impact patients’ outcome. In comparison to previous research, this suggests benefits from a higher dose.”
He added that “it would be interesting to test in this series if patients receiving more or less 30 Gy had different outcomes or the risks of failure at different sites.”
Overall, the study confirms that POAML “can be safely treated with radiation therapy, which allows for a better chance of local control, compared with other options, but does not preclude relapse over time,” Dr. Casasnovas concluded, adding, “I think that a standardization of radiotherapy dose is warranted to provide guidelines to clinicians treating this infrequent population of patients.”
The authors had no disclosures to report.
FROM ESMO 2023
Massive databases unleash discovery, but not so much in the U.S.
Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers.
A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?
Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery. 
“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.
Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care.
“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”
With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
Not so fast in the United States
In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal.
Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.
“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”
States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.
But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.
Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.
The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.
For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.
This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.
“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease.
For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors.
A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.
Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said.
Changes in the United States
The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases.
The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.
But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said.
“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”
A version of this article first appeared on Medscape.com.
Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers.
A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?
Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery.
“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.
Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care.
“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”
With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
Not so fast in the United States
In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal.
Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.
“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”
States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.
But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.
Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.
The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.
For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.
This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.
“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease.
For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors.
A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.
Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said.
Changes in the United States
The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases.
The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.
But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said.
“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”
A version of this article first appeared on Medscape.com.
Which conditions are caused by infection? Though it may seem like an amateur concern in the era of advanced microscopy, some culprits evade conventional methods of detection. Large medical databases hold the power to unlock answers.
A recent study from Sweden and Denmark meticulously traced the lives and medical histories of nearly one million men and women in those countries who had received blood transfusions over nearly five decades. Some of these patients later experienced brain bleeds. The inescapable question: Could a virus found in some donor blood have caused the hemorrhages?
Traditionally, brain bleeds have been thought to strike at random. But the new study, published in JAMA, points toward an infection that causes or, at the very least, is linked to the condition. The researchers used a large databank to make the discovery.
“As health data becomes more available and easier to analyze, we’ll see all kinds of cases like this,” said Jingcheng Zhao, MD, of the clinical epidemiology division of Sweden’s Karolinska Institutet in Solna and lead author of the study.
Scientists say the field of medical research is on the cusp of a revolution as immense health databases guide discovery and improve clinical care.
“If you can aggregate data, you have the statistical power to identify associations,” said David R. Crosslin, PhD, professor in the division of biomedical informatics and genomics at Tulane University in New Orleans. “It opens up the world for understanding diseases.”
With access to the large database, Dr. Zhao and his team found that some blood donors later experienced brain bleeds. And it turned out that the recipients of blood from those same donors carried the highest risk of experiencing a brain bleed later in life. Meanwhile, patients whose donors remained bleed-free had the lowest risk.
Not so fast in the United States
In Nordic countries, all hospitals, clinics, and pharmacies report data on diagnoses and health care visits to the government, tracking that began with paper and pen in the 1960s. But the United States health care system is too fragmented to replicate such efforts, with several brands of electronic medical records operating across different systems. Data sharing across institutions is minimal.
Most comparable health data in the United States comes from reimbursement information collected by the Centers for Medicare & Medicaid Services on government-sponsored insurance programs.
“We would need all the health care systems in the country to operate within the same IT system or use the same data model,” said Euan Ashley, MD, PhD, professor of genomics at Stanford (Calif.) University. “It’s an exciting prospect. But I think [the United States] is one of the last countries where it’ll happen.”
States, meanwhile, collect health data on specific areas like sexually transmitted infection cases and rates. Other states have registries, like the Connecticut Tumor Registry, which was established in 1941 and is the oldest population-based cancer registry in the world.
But all of these efforts are ad hoc, and no equivalent exists for heart disease and other conditions.
Health data companies have recently entered the U.S. data industry mainly through partnerships with health systems and insurance companies, using deidentified information from patient charts.
The large databases have yielded important findings that randomized clinical trials simply cannot, according to Dr. Ashley.
For instance, a study found that a heavily-lauded immunotherapy treatment did not provide meaningful outcomes for patients aged 75 years or older, but it did for younger patients.
This sort of analysis might enable clinicians to administer treatments based on how effective they are for patients with particular demographics, according to Cary Gross, MD, professor at Yale University in New Haven, Conn.
“From a bedside standpoint, these large databases can identify who benefits from what,” Dr. Gross said. “Precision medicine is not just about genetic tailoring.” These large datasets also provide insight into genetic and environmental variables that contribute to disease.
For instance, the UK Biobank has more than 500,000 participants paired with their medical records and scans of their body and brain. Researchers perform cognitive tests on participants and extract DNA from blood samples over their lifetime, allowing examination of interactions between risk factors.
A similar but much smaller-scale effort underway in the United States, called the All of Us Research Program, has enrolled more than 650,000 people, less than one-third the size of the UK Biobank by relative populations. The goal of the program is to provide insights into prevention and treatment of chronic disease among a diverse set of at least one million participants. The database includes information on sexual orientation, which is a fairly new datapoint collected by researchers in an effort to study health outcomes and inequities among the LGBTQ+ community.
Dr. Crosslin and his colleagues are writing a grant proposal to use the All of Us database to identify genetic risks for preeclampsia. People with certain genetic profiles may be predisposed to the life-threatening condition, and researchers may discover that lifestyle changes could decrease risk, Dr. Crosslin said.
Changes in the United States
The COVID-19 pandemic exposed the lack of centralized data in the United States because a majority of research on the virus has been conducted abroad in countries with national health care systems and these large databases.
The U.S. gap spurred a group of researchers to create the National Institutes of Health–funded National COVID Cohort Collaborative (N3C), a project that gathers medical records from millions of patients across health systems and provides access to research teams investigating a wide spectrum of topics, such as optimal timing for ventilator use.
But until government or private health systems develop a way to share and regulate health data ethically and efficiently, significant limits will persist on what large-scale databases can do, Dr. Gross said.
“At the federal level, we need to ensure this health information is made available for public health researchers so we don’t create these private fiefdoms of data,” Dr. Gross said. “Things have to be transparent. I think our country needs to take a step back and think about what we’re doing with our health data and how we can make sure it’s being managed ethically.”
A version of this article first appeared on Medscape.com.
Frontline myeloma treatments: ASCT vs. CAR T
“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.
Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.
Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.
Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.
Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.
Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.
“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.
A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”
Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.
“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.
Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.
Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.
Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.
Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.
Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.
“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.
A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”
Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.
“In an otherwise healthy treatment-naive patient with multiple myeloma, to ensure the best chances of overall survival, I would always recommend standard of care consolidation therapy of chemotherapy + ASCT,” said Sergio Giralt, MD, of New York’s Memorial Sloan Kettering Cancer Center, debating the merits of ASCT versus CAR T as consolidation therapy at the Lymphoma, Leukemia & Myeloma (LLM) Congress 2023 in New York.
Final results from the phase II GRIFFIN trial highlight the benchmarks that CAR T-cell therapy would need to reach to achieve equivalence with ASCT. At a 4-year follow-up, newly diagnosed MM patients who received daratumumab, lenalidomide, bortezomib, and dexamethasone (D-RVd) followed by ASCT + D-RVd consolidation, and daratumumab maintenance, had a progression-free survival (PFS) rate of 87.3%, 92.7% overall survival (OS) rate, and 50% achieved minimal residual disease negativity.
Dr. Adriana Rossi, MD, assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York, cited a convergence of evidence suggesting that CAR T could achieve impressive results as a consolidation therapy in fit patients with MM, including: CARTITUDE 1 and CARTITUDE 4, which studied CAR T in RR MM patients. However, due to the fact that no head-to-head study of CAR T vs. ASCT as consolidation therapy in otherwise healthy MM patients exists, “There is not enough long-term data to support the equivalence CAR T with ASCT,” Dr. Giralt concluded.
Dr. Rossi further advocated for considering CAR T as a consolidation treatment because of the risks of secondary malignancies associated with ACST maintenance regimens.
Dr. Giralt rebutted this argument by citing data about averse events (AE) in studies of CAR-T therapies in RR MM patients like KarMMa-2, in which grade 3-4 neutropenia, anemia, and thrombocytopenia occurred in 94.6%, 45.9%, and 37.8% of patients respectively. Furthermore, 2 of 37 patients in KarMMA died (1 pneumonia, 1 pseudomonal sepsis), while rates of death from AEs related to ASCT occur in less than 1% of patients, according to Dr. Giralt.
Beyond a dearth of evidence thus far about the long term PFS, OS, and safety profile superiority of CAR-T therapies, compared with ASCT in treatment-naive MM patients, Dr. Giralt also noted the facts that CAR T-cell therapies are expensive and require manufacturing infrastructure also demonstrate that they cannot be easily adopted everywhere, even as a third-line therapy.
“In many places like Morocco, where I practice, we do not have access to CAR-T therapies,” said Sadia Zafad, MD, of the Clinique Al Madina Hematology and Oncology Center in Casablanca, Morocco. Dr. Zafad attended the debate.
A lack of access to CAR T is also a problem in the United States, where wait times for the therapy can stretch up to 6 months, getting insurance approval is challenging, and many patients simply don’t live near a center where CAR T-cell therapy is available. Citing all these factors, Dr. Giralt concluded: “Even if CAR T can be shown to have the same results as transplant, it is much more resource-intensive than transplant, and insurers are going to start saying there’s no necessary benefit. We have yet to use value as a primary end point, but as cancer care gets more and more expensive, that’s going to come up more, for CAR T and other novel therapies.”
Dr. Giralt reported relationships with Actinuum, Amgen, BMS, Celgene, Crisper, J&J, Jazz, Kite, Miltenyi, Novartis, Sanofi, and Takeda. Dr. Rossi disclosed ties with Adaptive, BMS, Celgene, JNJ, Sanofi & Genzyme. Dr. Zafad reported no disclosures.
AT LLM CONGRESS 2023
FDA OKs ivosidenib for IDH1-mutated myelodysplastic syndromes
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
The agency also approved the Abbott RealTime IDH1 Assay to test for the mutation.
Almost 4% of the 16,000 people diagnosed with MDS in the United States each year carry an isocitrate dehydrogenase-1 (IDH1) mutation, which increases their risk for poor outcomes, such as transformation to acute myeloid leukemia, Servier explained in a press announcement.
Ivosidenib is an IDH1 inhibitor that has previously been approved for IDH1-mutated AML and locally advanced or metastatic cholangiocarcinoma. The new approval makes it the only targeted therapy approved for relapsed or refractory MDS with the mutation, Servier said.
The FDA approval was based on a phase 1 study in 18 adults aged 61-82 years with IDH1-mutated relapsed or refractory MDS. Patients started at a dose of 500 mg daily in 28-day cycles until disease progression, unacceptable toxicity, or hematopoietic stem cell transplantation. Median treatment duration was 9.3 months, and one patient went on to receive a transplant.
Overall survival was a median of 35.7 months. Fifteen patients (83.3%) had an objective response and 7 (38.9%) went into complete remission after a median of 1.9 months of treatment. The median duration of remission had not been reached at data cutoff.
Among the 9 patients dependent on RBC or platelet transfusions at baseline, 6 (66.7%) no longer needed them during any 56-day post-baseline period.
Grade 3/4 adverse events in 5% or more of patients included arthralgia, hypertension, fatigue, mucositis, and leukocytosis.
Labeling carries a boxed warning of potentially fatal differentiation syndrome. Ivosidenib can also cause QTc prolongation.
A version of this article first appeared on Medscape.com.
FDA proposes ban on hair straightener ingredients
The
The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.
One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.
Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.
Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.
“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”
A version of this article appeared on WebMD.com
The
The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.
One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.
Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.
Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.
“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”
A version of this article appeared on WebMD.com
The
The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.
One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.
Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.
Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.
“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”
A version of this article appeared on WebMD.com
Artificial intelligence in the office: Part 2
In the year since generative artificial intelligence (AI) software first began to emerge for use, the staggering pace and breadth of development has condensed years of growth and change into months and weeks. Among the settings where these tools may find the greatest straight-line relevance is private medical practice.
. A multitude of generative AI products with potential medical applications are now available, with new ones appearing almost weekly. (As always, I have no financial interest in any product or service mentioned in this column.)
Last month, I discussed ChatGPT, the best-known AI algorithm, and some of its applications in clinical practice, such as generating website, video, and blog content. ChatGPT can also provide rapid and concise answers to general medical questions, like a search engine – but with more natural language processing and contextual understanding. Additionally, the algorithm can draft generic medical documents, including templates for after-visit summaries, postprocedure instructions, referrals, prior authorization appeal letters, and educational handouts.
Another useful feature of ChatGPT is its ability to provide accurate and conversational language translations, thus serving as an interpreter during clinic visits in situations where a human translator is not available. It also has potential uses in clinical research by finding resources, formulating hypotheses, drafting study protocols, and collecting large amounts of data in short periods of time. Other possibilities include survey administration, clinical trial recruitment, and automatic medication monitoring.
GPT-4, the latest version of ChatGPT, is reported to have greater problem-solving abilities and an even broader knowledge base. Among its claimed skills are the ability to find the latest literature in a given area, write a discharge summary for a patient following an uncomplicated surgery, and an image analysis feature to identify objects in photos. GPT-4 has been praised as having “the potential to help drive medical innovation, from aiding with patient discharge notes, summarizing recent clinical trials, providing information on ethical guidelines, and much more.”
Bard, an AI “chat bot” introduced by Google earlier this year, intends to leverage Google’s enormous database to compete with ChatGPT in providing answers to medical questions. Bard also hopes to play a pivotal role in expanding telemedicine and remote care via Google’s secure connections and access to patient records and medical history, and “facilitate seamless communication through appointment scheduling, messaging, and sharing medical images,” according to PackT, a website for IT professionals. The company claims that Bard’s integration of AI and machine learning capabilities will serve to elevate health care efficiency and patient outcomes, PackT says, and “the platform’s AI system quickly and accurately analyzes patient records, identifies patterns and trends, and aids medical professionals in developing effective treatment plans.”
Doximity has introduced an AI engine called DocsGPT, an encrypted, HIPAA-compliant writing assistant that, the company says, can draft any form of professional correspondence, including prior authorization letters, insurance appeals, patient support letters, and patient education materials. The service is available at no charge to all U.S. physicians and medical students through their Doximity accounts.
Microsoft has introduced several AI products. BioGPT is a language model specifically designed for health care. Compared with GPT models that are trained on more general text data, BioGPT is purported to have a deeper understanding of the language used in biomedical research and can generate more accurate and relevant outputs for biomedical tasks, such as drug discovery, disease classification, and clinical decision support. Fabric is another health care–specific data and analytics platform the company described in an announcement in May. It can combine data from sources such as electronic health records, images, lab systems, medical devices, and claims systems so hospitals and offices can standardize it and access it in the same place. Microsoft said the new tools will help eliminate the “time-consuming” process of searching through these sources one by one. Microsoft will also offer a new generative AI chatbot called the Azure Health Bot, which can pull information from a health organization’s own internal data as well as reputable external sources such as the Food and Drug Administration and the National Institutes of Health.
Several other AI products are available for clinicians. Tana served as an administrative aid and a clinical helper during the height of the COVID-19 pandemic, answering frequently asked questions, facilitating appointment management, and gathering preliminary medical information prior to teleconsultations. Dougall GPT is another AI chatbot tailored for health care professionals. It provides clinicians with AI-tuned answers to their queries, augmented by links to relevant, up-to-date, authoritative resources. It also assists in drafting patient instructions, consultation summaries, speeches, and professional correspondence. Wang has created Clinical Camel, an open-source health care–focused chatbot that assembles medical data with a combination of user-shared conversations and synthetic conversations derived from curated clinical articles. The Chinese company Baidu has rolled out Ernie as a potential rival to ChatGPT. You get the idea.
Of course, the inherent drawbacks of AI, such as producing false or biased information, perpetuating harmful stereotypes, and presenting information that has since been proven inaccurate or out-of-date, must always be kept in mind. All AI algorithms have been criticized for giving wrong answers, as their datasets are generally culled from information published in 2021 or earlier. Several of them have been shown to fabricate information – a phenomenon labeled “artificial hallucinations” in one article. “The scientific community must be vigilant in verifying the accuracy and reliability of the information provided by AI tools,” wrote the authors of that paper. “Researchers should use AI as an aid rather than a replacement for critical thinking and fact-checking.”
In the year since generative artificial intelligence (AI) software first began to emerge for use, the staggering pace and breadth of development has condensed years of growth and change into months and weeks. Among the settings where these tools may find the greatest straight-line relevance is private medical practice.
. A multitude of generative AI products with potential medical applications are now available, with new ones appearing almost weekly. (As always, I have no financial interest in any product or service mentioned in this column.)
Last month, I discussed ChatGPT, the best-known AI algorithm, and some of its applications in clinical practice, such as generating website, video, and blog content. ChatGPT can also provide rapid and concise answers to general medical questions, like a search engine – but with more natural language processing and contextual understanding. Additionally, the algorithm can draft generic medical documents, including templates for after-visit summaries, postprocedure instructions, referrals, prior authorization appeal letters, and educational handouts.
Another useful feature of ChatGPT is its ability to provide accurate and conversational language translations, thus serving as an interpreter during clinic visits in situations where a human translator is not available. It also has potential uses in clinical research by finding resources, formulating hypotheses, drafting study protocols, and collecting large amounts of data in short periods of time. Other possibilities include survey administration, clinical trial recruitment, and automatic medication monitoring.
GPT-4, the latest version of ChatGPT, is reported to have greater problem-solving abilities and an even broader knowledge base. Among its claimed skills are the ability to find the latest literature in a given area, write a discharge summary for a patient following an uncomplicated surgery, and an image analysis feature to identify objects in photos. GPT-4 has been praised as having “the potential to help drive medical innovation, from aiding with patient discharge notes, summarizing recent clinical trials, providing information on ethical guidelines, and much more.”
Bard, an AI “chat bot” introduced by Google earlier this year, intends to leverage Google’s enormous database to compete with ChatGPT in providing answers to medical questions. Bard also hopes to play a pivotal role in expanding telemedicine and remote care via Google’s secure connections and access to patient records and medical history, and “facilitate seamless communication through appointment scheduling, messaging, and sharing medical images,” according to PackT, a website for IT professionals. The company claims that Bard’s integration of AI and machine learning capabilities will serve to elevate health care efficiency and patient outcomes, PackT says, and “the platform’s AI system quickly and accurately analyzes patient records, identifies patterns and trends, and aids medical professionals in developing effective treatment plans.”
Doximity has introduced an AI engine called DocsGPT, an encrypted, HIPAA-compliant writing assistant that, the company says, can draft any form of professional correspondence, including prior authorization letters, insurance appeals, patient support letters, and patient education materials. The service is available at no charge to all U.S. physicians and medical students through their Doximity accounts.
Microsoft has introduced several AI products. BioGPT is a language model specifically designed for health care. Compared with GPT models that are trained on more general text data, BioGPT is purported to have a deeper understanding of the language used in biomedical research and can generate more accurate and relevant outputs for biomedical tasks, such as drug discovery, disease classification, and clinical decision support. Fabric is another health care–specific data and analytics platform the company described in an announcement in May. It can combine data from sources such as electronic health records, images, lab systems, medical devices, and claims systems so hospitals and offices can standardize it and access it in the same place. Microsoft said the new tools will help eliminate the “time-consuming” process of searching through these sources one by one. Microsoft will also offer a new generative AI chatbot called the Azure Health Bot, which can pull information from a health organization’s own internal data as well as reputable external sources such as the Food and Drug Administration and the National Institutes of Health.
Several other AI products are available for clinicians. Tana served as an administrative aid and a clinical helper during the height of the COVID-19 pandemic, answering frequently asked questions, facilitating appointment management, and gathering preliminary medical information prior to teleconsultations. Dougall GPT is another AI chatbot tailored for health care professionals. It provides clinicians with AI-tuned answers to their queries, augmented by links to relevant, up-to-date, authoritative resources. It also assists in drafting patient instructions, consultation summaries, speeches, and professional correspondence. Wang has created Clinical Camel, an open-source health care–focused chatbot that assembles medical data with a combination of user-shared conversations and synthetic conversations derived from curated clinical articles. The Chinese company Baidu has rolled out Ernie as a potential rival to ChatGPT. You get the idea.
Of course, the inherent drawbacks of AI, such as producing false or biased information, perpetuating harmful stereotypes, and presenting information that has since been proven inaccurate or out-of-date, must always be kept in mind. All AI algorithms have been criticized for giving wrong answers, as their datasets are generally culled from information published in 2021 or earlier. Several of them have been shown to fabricate information – a phenomenon labeled “artificial hallucinations” in one article. “The scientific community must be vigilant in verifying the accuracy and reliability of the information provided by AI tools,” wrote the authors of that paper. “Researchers should use AI as an aid rather than a replacement for critical thinking and fact-checking.”
In the year since generative artificial intelligence (AI) software first began to emerge for use, the staggering pace and breadth of development has condensed years of growth and change into months and weeks. Among the settings where these tools may find the greatest straight-line relevance is private medical practice.
. A multitude of generative AI products with potential medical applications are now available, with new ones appearing almost weekly. (As always, I have no financial interest in any product or service mentioned in this column.)
Last month, I discussed ChatGPT, the best-known AI algorithm, and some of its applications in clinical practice, such as generating website, video, and blog content. ChatGPT can also provide rapid and concise answers to general medical questions, like a search engine – but with more natural language processing and contextual understanding. Additionally, the algorithm can draft generic medical documents, including templates for after-visit summaries, postprocedure instructions, referrals, prior authorization appeal letters, and educational handouts.
Another useful feature of ChatGPT is its ability to provide accurate and conversational language translations, thus serving as an interpreter during clinic visits in situations where a human translator is not available. It also has potential uses in clinical research by finding resources, formulating hypotheses, drafting study protocols, and collecting large amounts of data in short periods of time. Other possibilities include survey administration, clinical trial recruitment, and automatic medication monitoring.
GPT-4, the latest version of ChatGPT, is reported to have greater problem-solving abilities and an even broader knowledge base. Among its claimed skills are the ability to find the latest literature in a given area, write a discharge summary for a patient following an uncomplicated surgery, and an image analysis feature to identify objects in photos. GPT-4 has been praised as having “the potential to help drive medical innovation, from aiding with patient discharge notes, summarizing recent clinical trials, providing information on ethical guidelines, and much more.”
Bard, an AI “chat bot” introduced by Google earlier this year, intends to leverage Google’s enormous database to compete with ChatGPT in providing answers to medical questions. Bard also hopes to play a pivotal role in expanding telemedicine and remote care via Google’s secure connections and access to patient records and medical history, and “facilitate seamless communication through appointment scheduling, messaging, and sharing medical images,” according to PackT, a website for IT professionals. The company claims that Bard’s integration of AI and machine learning capabilities will serve to elevate health care efficiency and patient outcomes, PackT says, and “the platform’s AI system quickly and accurately analyzes patient records, identifies patterns and trends, and aids medical professionals in developing effective treatment plans.”
Doximity has introduced an AI engine called DocsGPT, an encrypted, HIPAA-compliant writing assistant that, the company says, can draft any form of professional correspondence, including prior authorization letters, insurance appeals, patient support letters, and patient education materials. The service is available at no charge to all U.S. physicians and medical students through their Doximity accounts.
Microsoft has introduced several AI products. BioGPT is a language model specifically designed for health care. Compared with GPT models that are trained on more general text data, BioGPT is purported to have a deeper understanding of the language used in biomedical research and can generate more accurate and relevant outputs for biomedical tasks, such as drug discovery, disease classification, and clinical decision support. Fabric is another health care–specific data and analytics platform the company described in an announcement in May. It can combine data from sources such as electronic health records, images, lab systems, medical devices, and claims systems so hospitals and offices can standardize it and access it in the same place. Microsoft said the new tools will help eliminate the “time-consuming” process of searching through these sources one by one. Microsoft will also offer a new generative AI chatbot called the Azure Health Bot, which can pull information from a health organization’s own internal data as well as reputable external sources such as the Food and Drug Administration and the National Institutes of Health.
Several other AI products are available for clinicians. Tana served as an administrative aid and a clinical helper during the height of the COVID-19 pandemic, answering frequently asked questions, facilitating appointment management, and gathering preliminary medical information prior to teleconsultations. Dougall GPT is another AI chatbot tailored for health care professionals. It provides clinicians with AI-tuned answers to their queries, augmented by links to relevant, up-to-date, authoritative resources. It also assists in drafting patient instructions, consultation summaries, speeches, and professional correspondence. Wang has created Clinical Camel, an open-source health care–focused chatbot that assembles medical data with a combination of user-shared conversations and synthetic conversations derived from curated clinical articles. The Chinese company Baidu has rolled out Ernie as a potential rival to ChatGPT. You get the idea.
Of course, the inherent drawbacks of AI, such as producing false or biased information, perpetuating harmful stereotypes, and presenting information that has since been proven inaccurate or out-of-date, must always be kept in mind. All AI algorithms have been criticized for giving wrong answers, as their datasets are generally culled from information published in 2021 or earlier. Several of them have been shown to fabricate information – a phenomenon labeled “artificial hallucinations” in one article. “The scientific community must be vigilant in verifying the accuracy and reliability of the information provided by AI tools,” wrote the authors of that paper. “Researchers should use AI as an aid rather than a replacement for critical thinking and fact-checking.”
Prior authorization software: Saves time but hurdles remain
New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices.
To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff.
After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.
“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.
For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.
So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.
There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.
Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
How it works
Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.”
In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.
The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.
“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”
This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.
Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.
In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.
Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.
At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
Automation hasn’t spread to practices yet
Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.
For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.
On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.
Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.
Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.
Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.
In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.
Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.
Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”
“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
Where does automation go from here?
Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.
Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.
Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.
Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.
EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.
The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.
Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
Will payers automate prior authorization?
Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.
Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).
Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.
The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.
Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.”
Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.
The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.
There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.
The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians.
Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.
A version of this article first appeared on Medscape.com.
New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices.
To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff.
After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.
“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.
For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.
So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.
There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.
Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
How it works
Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.”
In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.
The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.
“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”
This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.
Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.
In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.
Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.
At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
Automation hasn’t spread to practices yet
Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.
For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.
On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.
Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.
Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.
Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.
In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.
Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.
Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”
“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
Where does automation go from here?
Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.
Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.
Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.
Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.
EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.
The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.
Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
Will payers automate prior authorization?
Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.
Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).
Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.
The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.
Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.”
Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.
The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.
There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.
The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians.
Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.
A version of this article first appeared on Medscape.com.
New England Baptist Hospital has been grappling with a serious problem facing health care today: insurers demanding prior authorizations for services ordered by physicians. Meeting payers’ requirements eats up time, delays treatment, and can be a costly drain on doctors’ practices.
To deal with this problem, the Boston orthopedic hospital has opted to automate submission of prior authorization requests on behalf of more than 100 mostly orthopedic surgeons on staff.
After 5 years using this system, “we can say that automation definitely works,” said Lidiya Hadzhieva, director of patient access at the hospital. The software has reduced write-offs by 30% and staff costs by 25%. Prior authorization gets approved 3 days after scheduling, compared with 11 days previously, she said.
“This software not only saves staff time, but it can also more accurately predict when prior authorization is needed,” she added.
For practices deluged with required prior authorizations by insurers, automation is emerging as a way for practices to make the process less time-consuming and save money. However, the software can be costly and may not be adoptable to many practices, and many physicians are not even aware it exists.
So far, the software is mainly used at large organizations like hospital systems. But as word gets out and the software becomes easier to use, private practices and other smaller entities may join the automation trend.
There is definitely a need to automate prior authorization. The American Medical Association reports that physicians spend 16 hours per week on prior authorizations. In a recent AMA survey, more than 60% of physicians indicated that it’s difficult to know when prior authorization is needed. And 93% of physicians reported care delays while waiting for authorization, the AMA said.
Experts estimate that 80% of prior authorization work could be automated, but most practices still use the phone or fax, even as numbers of prior authorizations continue to increase.
How it works
Automation software connects directly to the practice’s electronic health record (EHR). “When the doctor places an order in the EHR, the process starts automatically,” Ms. Hadzhieva said. “The doctor may not even notice it.”
In addition to using an EHR connection, many software products can communicate with the payer through its portal or by fax or phone, while still automating other parts of the process.
The software’s first step is to decide whether prior authorization is needed. This requires having an updated list of the rules that each payer uses for prior authorization. Manually keeping track of payer rules is very time-consuming, but automation uses bots to visit each payer site to look for rules changes. One vendor, Infinitus, uses a voice-based bot called Eva that calls up each payer and speaks with a representative.
“Automatically updating payer rules is not a new technology,” said YiDing Yu, MD, chief product officer at Olive, the automation vendor for New England Baptist. “What is new in the last 5 years is extracting the information needed for the prior authorization out of the clinical notes.”
This is challenging because each doctor has different ways to describe each step of clinical work. To identify this shorthand, Dr. Yu said Olive uses natural language processing, which is a form of artificial intelligence that learns how each doctor describes things.
Dr. Yu asserts that Olive is actually better than a practice’s staff at digging out clinical information. She said staff without much clinical training may miss terms that the software can catch, and they don’t have the time to go back many months into the record to find valuable information. But automation can do that.
In some instances, however, the software may not be able to find the information, in which case it alerts staff through a prompt in the EHR and the information is retrieved manually, Dr. Yu said.
Next, the Olive software puts the information it found into the request form and sends it to the payer. After submission, the software constantly checks on the status of each request, again visiting payer sites with a bot.
At New England Baptist, the software is used mainly by physicians in fairly small private practices who are on staff. They are using the software on the hospital’s dime, but it only works inside the hospital, Ms. Hadzhieva said. For their work outside of the hospital, they would have to purchase the Olive software on their own, she said.
Automation hasn’t spread to practices yet
Despite the promising outcomes for products like Olive, automation software is still primarily used by large organizations. Vendors say very few private practices have bought it yet. “The technology works, but it is still in the early-adopter phase,” Dr. Yu said.
For one thing, the software can be expensive. Very few vendors reveal their prices, but Dr. Yu did so. She said Olive normally costs about $50,000 a year for even a small organization. She insisted, however, that the savings from avoiding just one denial each month for a hip surgery would justify the expense.
On the other hand, some automation software is free, such as the Surescripts product for prior authorization of prescriptions. But it is unclear whether Surescripts does as much as Olive. Vendors’ descriptions of their products tend to be vague.
Also, Surescripts and Olive have entirely separate functions. Dr. Yu said Olive is limited to procedures, so it benefits specialties like oncology, neurosurgery, colorectal surgery, vascular surgery, and cardiology. Olive does not cover prescriptions, because they operate on a different technology.
Dr. Yu said another hurdle for adopting the software is the kind of EHR systems that doctors use. At this point, only a few EHR systems – such as Epic, Cerner, and Athena – are compatible with Olive. Large organizations tend to use Epic and Cerner, while many practices often use Athena or a variety of other systems, she said.
Despite stunted demand, there is no shortage of companies offering automation software for medical (that is, non-prescription) prior authorization. One compilation lists 25 such vendors, including companies like Myndshft, Rhyme, Infinitus, Infinx, and Waystar. As with any start-up technology, companies occasionally buy each other out.
In addition to issues like cost, specialty, and EHR compatibility, another hurdle is that few doctors even know the technology exists. Vendors say marketing focuses on larger provider organizations, not smaller practices.
Even many tech-savvy doctors, like Adam Bruggeman, MD, an orthopedist and CEO of Texas Spine Care Center in San Antonio, say they know little about the technology. “There is definitely a need to automate prior authorization,” he said. “But I don’t know of any colleagues who use it.” He has only just begun to explore vendors, he said.
Many medical practice consultants also have not yet explored the technology. “Automation makes a lot of sense, because there are a lot of repetitive tasks in prior authorization,” said Jill Arena, CEO of Portland, Ore.–based Health e Practices. “But I haven’t looked into it yet, and none of my clients has even asked about it.”
“I could see how it could be an easier sell for large organizations,” she added. “They have an IT person and a CFO who can explore the issue. Smaller practices usually don’t have that kind of expertise.”
Where does automation go from here?
Until now, clinicians who want to fully automate prior authorizations would have to buy two products – one for medical procedures and one for prescriptions. This has to do with incompatible electronic transmission standards, which are used to digitize information, said Susan Lawson-Dawson, content marketing strategist for the vendor Myndshft Health.
Myndshft has long been selling automation software for medical prior authorizations, but now it is introducing a product for prescriptions, Ms. Lawson-Dawson said. She said Myndshft will then be the only vendor to automate both kinds of prior authorizations.
Ms. Lawson-Dawson said Myndshft has 685 customers to date and is looking for more business. Recently the company entered the Google Cloud Marketplace. Google Cloud customers can now direct their committed spend with Google to purchasing Myndshft, meaning they could get it at a discount.
Software like Olive and Myndshft can operate independently of payers, but a vendor called Rhyme depends on payers for its software to function, said Rhyme CEO Joe Anstine. He said more than 300 payers have agreed to install the Rhyme system, and Rhyme has signed up a number of large health systems to use the product. Initially, he said, clinicians paid for the service, but now Rhyme is beginning to find payers to foot the costs and to let clinicians use it for free, which would open Rhyme up to smaller practices.
EHR companies themselves are beginning to offer automation, too. Epic, for example, has created a tool for prior authorization as part of its Epic Payer Platform. Like Rhyme, it requires payer cooperation, because information goes back and forth between clinician and payer in what is called bi-directional exchange.
The Epic product is still in its pilot phase. Epic reported that several large health systems were using its product in conjunction with a specific payer – for instance, Mayo Clinic with Blue Cross and Blue Shield of Minnesota and Ochsner Health with Humana. According to Epic, the arrangement reduced Mayo’s denials due to additional documentation requests by 63% for professional billing.
Automating with just one payer still means the clinician has to deal with manual processes at other payers, but a large clinician could have sufficient volume with that one payer to make the arrangement useful.
Will payers automate prior authorization?
Ultimately, payers may take the automation business away from vendors, offering a free product to all clinicians. But don’t hold your breath. Payers first have to rebuild their electronic systems to accommodate an electronic connection with providers. Even then, some payers might hold back from automating, forcing practices to continue manually processing some prior authorizations.
Efforts are underway, however, to mandate payers to support prior authorization automation. For this to happen, payers would have to revamp their data so that it could be easily read by practices’ EHRs. This would mean adopting a specific interoperability standard called Health Level 7 Fast Healthcare Interoperability Resources (FHIR).
Toward this goal, the Centers for Medicare & Medicaid Services proposes to require payers to adopt FHIR by January 2026. (CMS still has to finalize the rule.) Experts say the two-year ramp-up time is needed because it takes extensive work for payers to translate their data into FHIR.
The only payer so far to switch to FHIR for prior authorization is Regence in Washington state. In a pilot project, it has automated prior authorization with just one provider, MultiCare Connected Care, an accountable care organization (ACO), also in Washington state.
Anna Taylor, associate vice president of population health and value-based care at MultiCare, explained how the arrangement works. “Two separate entities are sharing one operational process,” she told this news organization. “That means they can have a digital conversation back and forth, so it is much easier to resolve prior authorization issues.”
Unlike many vendor products, the Regence service is free. And while the vendors market only to large organizations, most doctors in the MultiCare arrangement are in independent practices. Ms. Taylor said these doctors have been “enthusiastic” about the arrangement.
The results of the pilot are impressive. Ms. Taylor said automation has resulted in a 233% productivity gain for MultiCare clinicians, and 89% of submissions to Regence get an immediate response.
There is a potential downside, however, to working directly with payers. A direct connection to clinicians allows payers to access the doctor’s clinical notes, which could make many doctors uneasy. But Ms. Taylor said Regence only has access to the “discrete data fields” on MultiCare’s EHR dashboard, not to the notes themselves.
The ultimate goal of the Regence-Multicare project is to include more payers and clinicians. Ms. Taylor said two of the 27 other payers that MultiCare works with are “highly interested,” but it would take a lot of work for them to get connected with practices and other clinicians.
Ultimately, payers could offer automation and third-party vendors might then fade away. However, physicians may resist working directly with payers if the arrangement requires full access to their medical records.
A version of this article first appeared on Medscape.com.