Study Compares Punch Excision vs. Core Excision for Recalcitrant Keloids

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Mon, 10/28/2024 - 12:03

Punch excision (PE) followed by immediate cryotherapy could be a viable and simpler alternative to core excision (CE) for the treatment of recalcitrant keloids, according to the results of a small retrospective study.

The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.

For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.

Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).

“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”

He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.

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

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Punch excision (PE) followed by immediate cryotherapy could be a viable and simpler alternative to core excision (CE) for the treatment of recalcitrant keloids, according to the results of a small retrospective study.

The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.

For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.

Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).

“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”

He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.

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

Punch excision (PE) followed by immediate cryotherapy could be a viable and simpler alternative to core excision (CE) for the treatment of recalcitrant keloids, according to the results of a small retrospective study.

The method “offers similar efficacy, faster healing, and fewer complications,” one of the study authors, Jinwoong Jung, MD, said in an interview following the annual meeting of the American Society for Dermatologic Surgery, where he presented the study results during an oral abstract session.

For the study, Jung, a dermatologist at Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively analyzed 22 patients with recalcitrant keloids treated with cryotherapy immediately following either PE or CE between May 2019 and March 2024. They used the Vancouver Scar Scale (VSS) to assess treatment efficacy.

Of the 22 patients, 16 underwent treatment with CE and 6 underwent treatment with PE. Pretreatment VSS scores showed no significant differences between the groups (P = .535). The CE group had a reduction in the VSS score from 8.13 to 4.00, while the PE group had a reduction from 7.83 to 3.67, but these declines did not differ significantly (P = .737). The PE group exhibited a shorter healing time than the CE group (a mean of 43.5 vs 63.87 days, respectively), though this difference was not statistically significant (P = .129).

“The uniqueness of this work lies in its simplified use of PE for recalcitrant keloids, which demonstrated efficacy comparable to CE, with the potential advantage of faster healing times,” Jung said. “Future studies with larger sample sizes and extended follow-up periods could help establish this approach as a standard treatment method.”

He acknowledged certain limitations of the study, including its small sample size and the lack of long-term follow-up data. The researchers reported having no relevant disclosures.

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

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Neurologists Lack Awareness of Steroid Toxicity

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Mon, 10/28/2024 - 09:45

There is a lack of understanding among neuromuscular specialists on how to balance the risks for and benefits of corticosteroids when treating patients with generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP), results of a US survey showed.

For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.

The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.

Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.

The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Lack of Knowledge

Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.

Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.

The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.

To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.

CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.

The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.

Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
 

Appropriate Dosing

When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.

“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.

“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”

Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.

When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.

Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
 

‘A Big Issue’ in Neurology

Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.

These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.

Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.

“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.

Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.

“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”

The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
 

A version of this article appeared on Medscape.com.

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There is a lack of understanding among neuromuscular specialists on how to balance the risks for and benefits of corticosteroids when treating patients with generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP), results of a US survey showed.

For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.

The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.

Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.

The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Lack of Knowledge

Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.

Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.

The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.

To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.

CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.

The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.

Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
 

Appropriate Dosing

When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.

“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.

“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”

Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.

When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.

Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
 

‘A Big Issue’ in Neurology

Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.

These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.

Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.

“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.

Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.

“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”

The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
 

A version of this article appeared on Medscape.com.

There is a lack of understanding among neuromuscular specialists on how to balance the risks for and benefits of corticosteroids when treating patients with generalized myasthenia gravis (gMG) and chronic inflammatory demyelinating polyneuropathy (CIDP), results of a US survey showed.

For both MG and CIDP specialists, uncertainty around corticosteroid dosing, duration, and toxicity underscores the need for more guidance, the investigators noted. Over 85% of respondents indicated that a tool for systematically monitoring corticosteroid toxicity would be valuable.

The results indicate “a lack of knowledge by this pool of neurologists about the guidelines and what they contain,” said study investigator Gil Wolfe, MD, professor of neurology at the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, in New York.

Clearer guidance on how to administer corticosteroids and manage toxicities in patients with gMG and CIDP “would be welcomed by neurologists and have potential for benefit to patient care,” the team noted.

The findings were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Lack of Knowledge

Although guidelines for both CIDP and gMG recommend corticosteroids as first-line treatment and emphasize using the lowest effective dose to control symptoms, they do not include specific recommendations on dosing, duration, or toxicity monitoring, the researchers noted.

Despite this, a large proportion of survey respondents reported using guidelines to make clinical decisions on monitoring toxicity, with up to a third actually endorsing a guideline that doesn’t exist.

The cross-sectional, online survey was deployed in November and December 2023 and included 200 US neurologists. Of these, 99 answered questions on CIDP, and 101 answered similar questions on gMG.

To participate in the survey, respondents had to be board-certified neurologists, practicing for at least 2 years post-residency, and have treated or consulted on at least three patients with CIDP or 10 patients with gMG in the past year who were on a corticosteroid dose of at least 10 mg daily for 1 month or more.

CIDP respondents had been practicing a mean of 18.1 years since residency and were board certified in neuromuscular (20%), electrodiagnostic medicine/clinical neurophysiology (21%), and pediatric neurology (8%). Two thirds of them accepted referrals from other neurologists.

The gMG respondents had been practicing a mean of 20.5 years since residency and were board certified in neuromuscular (45%), electrodiagnostic medicine/clinical neurophysiology (35%), and pediatric neurology (17%). A total of 72% accepted referrals from other neurologists.

Respondents estimated that about 60% of their patients with gMG and 58% of patients with CIDP were being treated with corticosteroids, with gMG and CIDP respondents reporting a mean of 26.4 and 15.6 patients, respectively, meeting the study’s dosing criteria.
 

Appropriate Dosing

When asked what chronic, long-term (≥ 6 months) corticosteroid dose they considered safe in terms of minimizing adverse events, 43% of CIDP respondents and 51% of gMG respondents considered corticosteroid doses of 10 mg/d or less (prednisone equivalent) well tolerated; additionally, 32% and 31%, respectively, considered 20-40 mg/d well tolerated. Moreover, they said only about half of their patients would be able to taper to less than 10 mg/d in less than 6 months.

“Studies suggest safety is not seen until patients are on doses at 5 mg/d or less,” Wolfe said. “There is not enough appreciation that doses at levels we once considered safe really do pose significant risk,” he added.

“With the increasing number of treatment options in MG and to a lesser extent in CIDP, we need to do all we can to use corticosteroids as judiciously as possible and be aware of side effects our patients may not even report unless we make a pointed effort to ask about them.”

Familiarity with corticosteroid toxicities was more common among gMG respondents, of whom 77% reported being very/extremely familiar, than among 55% of CIDP respondents. Appetite/weight gain was reported among the most common adverse effects (AEs) associated with long-term CS use (reported by 68% of CIDP and 58% of gMG respondents). Other common AEs reported were insulin resistance (53% of CIDP and 50% of gMG respondents), decreased bone density (47% and 48%, respectively), immunosuppression (37% and 45%, respectively). Mood and behavioral change were noted by 56% of CIDP and 37% of gMG respondents, particularly mood swings, irritability, mania, and sleep disorders.

When asked how they balanced the risk for and benefit of corticosteroids, more than 80% of CIDP specialists reported personally monitoring for corticosteroid-related toxicity, and 42% reported they collaborated with the patient’s primary care provider. However, fewer than 10% reported ordering lab tests. Among neurologists treating gMG, 84% said they typically monitor corticosteroid toxicity independently, while 41% reported doing so in collaboration with primary care providers.

Two thirds of CIDP respondents and 53% of gMG respondents reported using guidelines to make clinical decisions on monitoring toxicity, and 34% of gMG respondents actually endorsed using the Guideline for Systematic Surveillance of Steroid Safety, which does not exist.
 

‘A Big Issue’ in Neurology

Commenting on the results, Said R. Beydoun, MD, professor and division chief, Neuromuscular Medicine, Department of Neurology at Keck Medicine of University of Southern California, Los Angeles, said steroid toxicity is “a big issue” in neurology.

These patients can be on chronic therapy, and they aren’t really monitored for osteoporosis or other complications, he said, adding that neurologists aren’t always taking the necessary precautions to prevent steroid toxicity.

Beydoun estimated that about half of neurologists are not adequately familiar with balancing the efficacy of corticosteroids versus in toxicity.

“Objective improvement, either on the functional scale or the muscle impairment scale — that’s really response treatment. Whereas adverse effects of a treatment are something separate. The patient may be improving but also maybe developing other complications from the treatment,” he said.

Also commenting, Ghazala Hayat, MD, professor of neurology and director of neuromuscular and clinical neurophysiology services at Saint Louis University in St. Louis, said there is a clear need for more education.

“I always say prednisone is our best friend initially, and then it becomes the worst enemy. If you don’t see lots of neuromuscular patients, you might not know even how to recognize toxicity or how to taper. Or the opposite to that, if you taper too quickly, patients relapse.”

The study was funded by argenx. Wolfe reported serving on advisory boards for Alexion, argenx, UCB, and Johnson & Johnson. Neelam Goyal, MD, is a consultant/advisor for Alexion, argenx, Amgen, Janssen, Lycia Therapeutics, and UCB and has received grant support from argenx. Beydoun reported receiving research support and consulting and speaking fees from Healey Center, Amylyx, AB Science, Sanofi, Janssen, Genentech, Regeneron, UCB, Abcuro argenx, Alnylam, AstraZeneca, Amylyx, CSL Behring, Grifols, Takeda, Octapharma, UCB, and Janssen. Hayat reported speaker and advisory roles with argenx, Alexion, and MTPA.
 

A version of this article appeared on Medscape.com.

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Veterans Affairs Hailed as a ‘Bright Spot’ in ALS Care

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Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

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Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

Teamwork and transdisciplinary collaboration create an effective system of care for amyotrophic lateral sclerosis (ALS), ensuring improved health both for patients and clinicians alike, said one expert.

In a plenary address at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024, Ileana Howard, MD, medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, said the recently released National Academies report “Living with ALS” cited the Veterans Administration as “a bright spot in the landscape of ALS care due to its interdisciplinary, holistic, and proactive approach to care.”

Since the early 2000s and the publication of several studies linking active military service with ALS, the US Department of Veterans Affairs (VA) has opened an ALS registry, a tissue and brain biobank, and in 2008, granted 100% presumptive service connection to any individual who served more than 90 days of active duty and was later diagnosed with ALS, she said.

“We now serve approximately 4000 veterans with ALS across the system, and we count 47 full interdisciplinary clinics within VA across the nation, with ALS coordinators designated for all 170 VA facilities, regardless of whether they had an ALS clinic or not, to serve as a navigator for patients and their families, to identify the closest ALS clinic that could meet their needs.” 
 

Multidisciplinary vs Interdisciplinary

Howard emphasized that transdisciplinary collaboration is essential for maintaining an effective system. She pointed out that the term “multidisciplinary” is outdated, referring to teams that work independently but in parallel on the same issue.

In contrast, interdisciplinary teams integrate their assessments into a cohesive plan of care, whereas transdisciplinary teams take it further by combining both their assessments and care plans, allowing for greater intentional overlap.

The VA’s ALS handbook lists approximately 20 essential clinicians for a VA ALS clinic, including recreation therapists, assistive technology specialists, and veteran benefit service officers to assist with disability benefits application, among others, she said.

Essential to this collaboration is “role release,” which deliberately blurs the boundaries between disciplines. “The future of our specialty hinges on effective and selfless collaboration,” she said.

Howard encouraged ALS healthcare providers to move away from outdated terminology rooted in hierarchical team models and to break down silos that no longer benefit either the patients or the care teams.

She noted that while teamwork can enhance patient outcomes and overall health, it has also been associated with better health among healthcare providers. It’s well-known, she said, that neurologists and physiatrists are among the specialties with the highest burnout rates, and ALS teams, in particular, experience significant stress and burnout.
 

Better Together

recent Canadian study on resiliency and burnout in ALS clinics surveyed a wide range of practitioners within ALS centers and found respondents drew resiliency through relationships with patients and colleagues, and that there was a strongly expressed desire for increased resources, team building/debriefing, and formal training in emotional exhaustion and burnout.

“A consistent theme was the lack of adequate allied health support (nursing, social work, occupational therapy) to address the complex needs of patients,” said the report’s senior author Kerri Lynn Schellenberg, MD, medical director of the ALS/Motor Neuron Diseases clinic and associate professor at the University of Saskatchewan College of Medicine in Saskatoon, Saskatchewan, Canada.

“The majority of participants felt they would benefit from more consistent team building exercises and debriefing,” noted the authors.

Schellenberg agreed, emphasizing that care teams perform best when there is mutual appreciation and support among members. By learning from one another and reaching consensus together, the care plan benefits from the collective expertise of the team. “We are stronger together,” she said.

Howard and Schellenberg reported no disclosures.
 

A version of this article appeared on Medscape.com.

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Digital Tool May Help Neurologists Assess Steroid Toxicity

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Mon, 10/28/2024 - 09:35

A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

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A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

A digital tool to help neurologists assess steroid toxicity in patients with myasthenia gravis (MG) demonstrated sensitivity in distinguishing between different doses and durations of steroid exposure in a retrospective, real-world study.

The Glucocorticoid Toxicity Index-Metabolic Domains (GTI-MD), an abbreviated version of the GTI (Steritas), used weighted, standardized clinical outcome assessments to calculate steroid toxicity using a de-identified electronic health record (EHR) dataset.

“The results of our study indicate that patients with MG who initiated steroids demonstrated evidence of steroid toxicity in as little as 90 days after initial exposure, which was significant for patients with 20+ mg at index with repeated use,” noted study investigators, led by Neelam Goyal, MD, clinical professor of neurology and neurological sciences at Stanford University School of Medicine in Palo Alto, California.

The findings were presented at American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
 

Rapid Evidence of Toxicity

The GTI uses nine health domains to calculate steroid toxicity scores, and the GTI-MD, which has been shown to be closely correlated, uses four domains collected routinely in clinical practice: Body mass index (BMI), blood pressure, glucose tolerance, and lipid metabolism.

The study used the Optum EHR dataset to identify 682 adult patients with MG, mean age of 70 years, 38% women, with at least two confirmed diagnoses of MG between 30 and 730 days apart and information on steroid utilization.

Patients were divided into two groups: Steroid initiators (SI; n = 377) were those whose steroid use was already in progress at the index date, whereas steroid-naive (SN) patients (n = 305) began their steroid use at the index date. Among the SI group, 30% were on doses greater than 20 mg/d and 22% were on lower doses. Among the SN group, 22% were on doses greater than 20 mg/d and 26% were on lower doses.

As expected, mean GTI-MD scores measured 90 days after the index date were higher in the SI group than in the SN group, indicating a higher level of steroid toxicity in the SI group. This was measured with two subscores of the GTI-MD: The Cumulative Worsening Score (22.6 vs 18.7; P = .007) and the Aggregate Improvement Score (4.9 vs 1.9; P = .27), the latter incorporating resolved toxicities resulting from the introduction of steroid-sparing agents.

The authors commented that scores were higher in the SN group than expected, “which could be explained by age, previous steroid exposure, comorbidities, and side effects from other medications.” However, they concluded that the findings suggest utility of the tool retrospectively, with EHR data.
 

Clinical Application

The GTI and related measurements are proprietary tools and therefore not readily available to all clinicians, noted Marie Beaudin, MD, another neurologist at Stanford University School of Medicine, who was not involved in the research.

In a separate, observational, ongoing study, Beaudin and Goyal’s team are examining the use of the tool prospectively for following the steroid toxicity burden in 50 patients with MG and correlating it with MG outcomes measured using the MG-Activities of Daily Living, MG Composite, and MG-Quality of Life 15R validated scales, as well as the adverse event unit.

“The objective of this study is to quantify the burden of toxicity that our patients are having from glucocorticoids, see how sensitive to change the scale is as their dosage of prednisone changes, and explore the correlations between the score and their disease outcome measures,” Beaudin said.

Unlike the abbreviated GTI-MD, the GTI measures nine domains: Bone mineral density, BMI, lipid metabolism, blood pressure, glucose tolerance, myopathy, skin toxicity, neuropsychiatric symptoms, and infections.

The score involves actively prompting and examining the patient, making it quite comprehensive. Beaudin said the study has revealed interesting insights into how patients report their side effects. When asked broadly about steroid-related side effects, many patients mention issues like weight or skin issues.

However, she noted, when prompted specifically about symptoms like insomnia, irritability, depression, or cognitive changes, there was an unexpected increase in positive responses, as patients are often unaware these could be side effects. This suggests the study may capture a greater burden than originally anticipated, said Beaudin.

She added that the long-term utility of the GTI score might be to help clinicians predict steroid toxicity and guide management.

“Then we would get more aggressive in trying to wean or taper patients. But these are often complicated cases because as soon as we taper, the disease flares. It’s a difficult decision whether to reduce the dosage of prednisone because toxicity burden is high, when disease burden is high too, and that’s where other medications can come into play.”

For example, she said, for insurance coverage, a high steroid toxicity score could justify the need to initiate more expensive steroid-sparing agents.

Both studies were funded by argenx. Goyal reported that she has consulted and received grant support from argenx, UCB, Alexion, and Janssen argenx. Beaudin is supported by a McLaughlin Scholarship from Laval University, Quebec, Canada.
 

A version of this article appeared on Medscape.com.

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Multi-Refractory MM: After Immunotherapy, What?

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Tue, 10/29/2024 - 15:45

 

— When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

 

 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

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— When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

 

 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

 

— When patients with multiple myeloma (MM) relapse following chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsABs), or both, likely salvage options remain that are being overlooked, including a second course of immunotherapy. Two independent experts, addressing this issue at the 2024 Lymphoma, Leukemia & Myeloma Congress, offered several practical recommendations for eliciting a therapeutic response after patients with multi-refractory MM have failed everything. One approach they endorsed was allowing patients to recover from T-cell exhaustion.

“We used to think that as soon as multiple myeloma patients progress on a CAR T-cell therapy, it was sort of game over,” said Joseph Mikhael, MD, professor, Translational Genomics Research Institute, City of Hope Cancer Center Phoenix, Arizona.

“But I think we are seeing many ways to salvage these patients, including going back to a CAR T product,” said Mikhael, who also serves as the chief medical officer of the International Myeloma Foundation.

Now that CAR T cells and BsABs are widely available, Mikhael warned that there will be a growing need for other strategies to offer when these therapies fail.

A similar point was made by Jorge Monge, MD, an assistant professor, Division of Hematology and Medical Oncology, Weill Cornell Medicine, New York City. He largely focused on newer therapies with the potential to provide salvage opportunities in advanced refractory MM, but he pointed out that one application might be to permit T-cell recovery after exhaustion following B-cell maturation antigen (BCMA)–targeted therapies.

The two talks covered some of the same ground. Both, for example, discussed a potential role for the exportin 1 (XPO1) inhibitor selinexor (Xpovio) in the multidrug refractory setting. In combination with bortezomib and dexamethasone, selinexor was approved in 2020 for treatment-experienced patients but is often overlooked in late-stage disease.

As a strategy to elicit a response following BCMA-targeted therapies, both Mikhael and Monge cited data showing selinexor to be active and that side effects are relatively well managed if antiemetics are offered preemptively to control nausea, one of its most common side effects.

Monge also talked about the promise of cereblon E3 ligase modulatory drugs (CELMoDs) that are now in clinical trials. These drugs, such as mezigdomide and iberdomide, both of which are in advanced stages of clinical testing, are similar to the immunomodulatory agents lenalidomide and pomalidomide. However, their greater potency does not appear to substantially increase risk for adverse events, according to Monge.
 

CELMoDs Active After CAR T-Cell Therapy

Most importantly, from the standpoint of their potential role in multidrug-refractory MM, both mezigdomide and iberdomide have so far shown substantial activity in patients previously exposed to BCMA-targeted therapies, according to Monge. Although the data have been generated in small numbers of patients, he reported that objective response rates have ranged from 37% to 50%.

These rates in treatment-experience patients are lower relative to those achieved in patients with no prior exposure to BCMA-targeted drugs, but Monge said that the durations of response, exceeding 6 months in some studies, might provide enough time for the T-cell recovery needed for a second course of CAR T-cell therapy.

There are other promising therapies on the horizon relevant to controlling multidrug refractory MM, including the likely return of the antibody drug conjugate (ADC) belantamab mafodotin (Blenrep®). This drug was withdrawn in 2022, when the DREAMM-3 trial failed to show an advantage on the primary endpoint of progression-free survival (PFS) for this drug alone over pomalidomide and dexamethasone. The failed results of the DREAMM-3 trial meant that the drug did not meet FDA requirements for confirmatory trials of drugs approved through the agency’s accelerated approval program.

However, recently published results from the phase 3 DREAMM-8 trial did show a PFS advantage for belantamab mafodotin, pomalidomide, and dexamethasone over pomalidomide, bortezomib, and dexamethasone at 12 months (HR 0.50; P < .0010). On the basis of this result and other positive findings, including a deeper response, Mikhael predicted that this drug will be reintroduced.

It “might take a year or more” to find its way through the approval process, but Mikhael said that he is among those who think it will have value in advanced MM.*

Many of the newer MM drugs, including bispecifics that engage proteins on the surface of the myeloma cell other than BCMA, such as G protein–coupled receptor family C group, might provide alternatives to BCMA-targeted therapies in late stages of disease, but at least some newer drugs, as well as existing drugs in combinations, might play an important role in refractory MM by restoring BCMA as a target.

“The BCMA target is not easily lost, and I think we can leverage it more than once,” Mikhael said.

This potential, which Mikhael acknowledged is mostly supported with relatively small sets of data, involves “a lot of question marks, a lot of maybes,” so the strategies are hard to compared. However, the “incredible evolution in multiple myeloma therapy” over the past few years is not necessarily linear, according to Mikhael.
 

 

 

Recycling MM Therapies Deserves Consideration

In other words, CAR T cells and BsABs are not the last stop in the available lines of therapy for MM. The next best therapy is dependent on numerous considerations, including prior therapy exposure, but Mikhael pointed out that many patients in advanced stages have not been exposed to therapies known to be active or are not being considered for therapies to which they were exposed but are not necessarily resistant.

Monge made similar comments. He agreed with Mikhael that clinicians faced with a patient with multitherapy-refractory MM might forget about the XPO1 inhibitor selinexor, the alkylating agent bendamustine, or even the B-cell lymphoma 2 inhibitor venetoclax.

Any of these agents alone or in combination could be considered to “give the patient some time to improve” T-cell function, Monge said.

This approach will have even more promise if better assays of T-cell function become available, Mikhael said. Although he explained that T-cell exhaustion is clearly one of the reasons that CAR T-cell therapies stop working, this cannot be measured accurately at this time.

“Better T-cell assays may help,” he said.

Mikhael reported financial relationships with Amgen, Bristol Myers Squibb, Janssen Pharmaceuticals, Karyopharm Therapeutics, Sanofi, and Takeda. Monge disclosed ties with Bristol Myers Squibb and Karyopharm Therapeutics.

*Correction, 10/29/24: We are correcting the name of the DREAMM-3 trial and clarifying that its failed results meant that the drug did not meet the FDA’s requirements for confirmatory trials of drugs to be approved through the agency’s accelerated approval program.
 

A version of this article appeared on Medscape.com.

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Lymphoma Debate: CAR T Not a Clear Winner

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— In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

 

 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

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— In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

 

 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

— In a three-way debate on whether to prioritize chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies (BsAbs), or one of the novel oral targeted therapies for relapsed/refractory follicular lymphoma (R/R FL), no expert conceded.

Acknowledging that hers was the weakest position, even the specialist who defended novel targeted therapies mounted a staunch defense of real-world patients being treated outside of tertiary centers.

“I was told by many of my colleagues that I got the short end of the stick in this debate, but I am actually here to convince everybody that targeted therapies continue to play an important role, despite the fact that they are the least sexy of these treatment options,” said Joanna Rhodes, MD, director of the Lymphoma Program at Rutgers Cancer Institute, Hoboken, New Jersey.
 

Targeted Therapies Still Relevant to Advanced FL

Although even the newest or coming targeted therapies, such as the EZH2 inhibitor tazemetostat or next-generation Bruton tyrosine kinase inhibitors, are not likely to achieve the deep responses and long-term progression-free survival possible with BsAbs or CAR T-cell therapy, the sustained disease control they offer for many patients with R/R FL is not trivial, according to Rhodes.

“The majority of these [advanced follicular lymphoma] patients are being managed in the community,” Rhodes argued at the 2024 Lymphoma, Leukemia, & Myeloma Congress. Access to tertiary centers where the most advanced therapies are available in some cases might not even be feasible. 

Moreover, there are barriers to CAR T cells and BsAbs even at centers where these are available, Rhodes said. On a long list of barriers, lack of caregiver support is an example of one common disqualification at her own institution. 

The experience with CAR T cells in R/R FL has been relatively short, so Rhodes used data on CAR T cells for B-cell lymphoma to make her point. It is not just that the proportion of eligible patients is limited. 

“The majority of B-cell lymphoma patients who are eligible for CAR T cells are not getting them,” she said. “It will be the same for FL.”

In other words, Rhodes indicated that it is premature to count out targeted oral agents or lenalidomide despite the excitement surrounding BsAbs and CAR T cells. The targeted agents and immunomodulatory drugs remain appropriate choices for patients unable or unwilling to travel to tertiary centers for treatment, for frail patients, and for well-informed patients who understand their options and still consider better tolerated therapies to be more consistent with their perception of an adequate risk-benefit ratio. 
 

BsAbs Vie With CAR T Cells in Advanced FL

Hers might be a valid summary, but it did not derail arguments about whether CAR T-cell therapy should be prioritized over BsAbs or the other way around for patients who are candidates for both. 

There are two BsAbs currently approved for R/R FL: glofitamab and mosunetuzumab. More are coming, according to Nina Wagner-Johnston, MD, director of hematologic malignancies at Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, Maryland. She provided several reasons why BsAbs might be considered before CAR T-cell therapies in at least some individuals. 

“The biggest advantage is that these therapies…are off the shelf,” she said. This avoids the delay of T-cell manufacturing, the potential need for bridging therapies, and the need for conditioning regimens. With more experience, BsAbs offer the potential for treatment even in a community-practice setting, particularly for maintenance dosing.

“I do think this is a safe treatment in patients who are elderly or unfit,” Wagner-Johnston said, suggesting she tends to lean toward prioritizing BsAbs over CAR T cells when the ability to tolerate an aggressive strategy is a concern. She specified that these drugs are associated with a low relative incidence of grade 3 or higher cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome, and faster B-cell aplasia recovery. 

The third participant in the debate, who described the efficacy and safety of the three currently approved CAR T-cell therapies for R/R FL, did not agree with this characterization. Daniel J. Landsburg, MD, associate professor of clinical medicine at the University of Pennsylvania, Philadelphia, acknowledged that BsAb agents have an important role to play in the advanced FL setting, but he thinks that CAR T-cell therapies should be prioritized in at least some patients. 

In particular, he would not rule out CAR T-cell therapy in patients with comorbidities or other characteristics that raise questions about fitness for aggressive treatment. 

“In fact, you might want to treat a frail patient just one time with CAR T-cell therapy rather than dose after dose with a bispecific drug,” he said. 
 

 

 

No Data to Compare BsAbs and CAR T-Cells Directly

Both agreed that there have been no trials directly comparing a BsAb therapy vs CAR T cells, so there is no definitive answer, and Landsburg was reluctant to take a hard line on reserving BsAbs until after CAR T-cell therapy has been tried.

“Because BsAbs and CAR Ts are approved in the third-line setting, you might consider debulking a patient getting ready for a CAR T with a bispecific,” Landsburg said. However, he acknowledged that the next step becomes complex if patients achieved a complete response after just a few BsAb doses.

“Do you stop what is already working?” Landsburg asked rhetorically, suggesting that the best way forward is not always clear.

For R/R FL, currently there are three approved products: axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi). The entry criteria and design of the three pivotal trials differed, so their specific indications vary. Looking across the trials, Landsburg suggested that there might be differences in activity as defined by objective response rates or risk for cytokine release syndrome, but these remain theoretical without head-to-head comparisons.

“My suspicion is we are going to see very similar — quote, unquote — long-term survival curves for patients treated with any of these therapies,” he said, noting that progression-free survival at 3 years has been in the vicinity of 50% for the trials that have had long enough follow-up to judge.

Rather than trying to pick the best agent, he suggested that it makes more sense now to concentrate on strategies to improve response irrespective of CAR T-cell product; these include paying attention to total metabolic tumor volume at the time of infusion, optimizing bridging therapies, and thinking about T-cell fitness, which might be impaired in some patients by recent exposure to bendamustine.

Overall, with multiple ongoing studies with both CAR T-cell therapies and BsAbs in R/R FL — as well with targeted small-molecule agents and immunomodulatory drugs — all of the debate participants acknowledged that choices in R/R FL will evolve. 

“I actually think that combinations will be the future,” Wagner-Johnston said. Singling out tazemetostat and a BsAb and one approach that seems promising, she also predicted that some of the therapies in advanced disease are likely to be moved forward to earlier stages of FL therapy.

Rhodes reported ties with AbbVie, AstraZeneca, ADC Therapeutics, BeiGene, Bristol Myers Squibb, Epizyme, Genentech, Genmab, Janssen, Loxo Oncology, MorphoSys, Pharmacyclics, and Pfizer. Wagner-Johnston disclosed relationships with Cuno Science, Dava Oncology, Epizyme, Grünenthal, Karyopharm, and Seagen. Landsburg reported ties with ADC Therapeutics, Calithera, Curis, Epizyme, Karyopharm, MorphoSys, and Novartis.
 

A version of this article appeared on Medscape.com.

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Expert Updates Therapy for Waldenström Macroglobulinemia

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— In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamidebortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

 

 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

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— In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamidebortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

 

 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

— In the wake of details about the molecular pathophysiology of Waldenström macroglobulinemia (WM), an expert gave an update on current and expanding options for treatment.

Most importantly, determining the mutational status of patients with WM has become a first or early step in guiding first- and second-line therapies, according to Edward A. Stadtmauer, MD, professor of medicine, University of Pennsylvania, Philadelphia.

Presenting at the 2024 Lymphoma, Leukemia & Myeloma Congress in New York City, Stadtmauer discussed how MYD88 and CXCR4 gene mutations influence his therapeutic choices.

While delivering the Bruce Waterfall Memorial Lecture, funded by the International WM Foundation, he explained that the vast majority of patients with WM have a MYD88 mutation that is highly sensitive to Bruton tyrosine kinase (BTK) inhibitors.

Due to greater specificity on the BTK target, which has implications for safety and efficacy, the first-generation BTK inhibitor ibrutinib has been largely supplanted by next generation drugs such as zanubrutinib.
 

Deep Responses in WM Remain Elusive

The support for next-generation BTK inhibitors over ibrutinib; bendamustine plus rituximab (BR); or cyclophosphamidebortezomib, and dexamethasone (CyBorD) is, in his opinion, “a superior toxicity profile, high response rates, and prolonged response.” However, he conceded that the weaknesses of this approach include a low chance of a deep remission and the need for continuous therapy.

On account of these limitations, he typically favors the alkylating agent bendamustine plus the anti-CD20 rituximab over BTK inhibitors in the absence of MYD88 mutations. This once standard approach has become less commonly used in the era of BTK inhibitors, but it is also highly effective, is generally administered in a time-limited regimen, and may be more likely to push patients into a deep remission.

A similar rationale might be considered for CyBorD, but Stadtmauer believes that BR provides a higher rate of PFS with a lower risk for neuropathy, although he admitted this opinion is based on cross-study comparisons, not comparative trials.

While efforts to develop therapies capable of producing a deep response “should not be abandoned,” particularly with the T-cell engager therapies on the horizon, he is not convinced that the benefit-to-risk ratio of aggressive therapies is yet warranted in a disease the often progresses slowly.

“I must admit I am still under the philosophy that Waldenström’s is a chronic disease even if we are seeing a growing list of options for relapsed or poorly responding disease, so I am still not pushing patients too aggressively to knock them into a complete remission,” he said.

MYD88 mutations are not unique to WM, an uncommon, slow-growing form of non-Hodgkin lymphoma. They are found in a small proportion of patients with other hematologic disorders, such as marginal zone lymphomas, but Stadtmauer estimated they occur in 90% of patients with WM. They are common enough that they can help with diagnosis.
 

CXCR4 Mutations Predict Worse Outcomes

The CXCR4 mutation occurs in an estimated 40% of patients with WM. When present, they are associated with worse outcomes, including a faster time to progression and a reduced overall survival, according to Stadtmauer.

The prognostic impact of less common mutations, such as TP53 and TERT or deletions in LYN, are less well characterized, but Stadtmauer said that most mutations associated with WM result in constitutive or continuous activation in BTK, which, in turn drives WM cell proliferation and survival.

The importance of BTK in WM progression is the reason targeted inhibitors have assumed such a key role in first-line treatment, but Stadtmauer cautioned that these drugs, like other therapies, should not be initiated in asymptomatic patients. This has been stated in past and current guidelines.

More accurately, therapy should be held until just prior to symptomatic manifestations of disease, Stadtmauer specified.

For an optimal response, “you want to start therapy about 3 or 4 months before the symptoms begin,” said Stadtmauer characterizing efforts to do so as “the art of medicine.” Starting therapy just prior to symptoms is advantageous, but it involves following patients closely. Any single biomarker might not be enough.

“In an asymptomatic patient, the level of monoclonal IgM is not an indication to start therapy,” he said, citing studies showing no effect on subsequent disease control from treating this biomarker alone.

However, he listed the development of moderate peripheral neuropathy (PN) as an exception. Essentially, anything greater than mild PN is “still bad” in Stadtmauer’s opinion, so treatment is warranted.

The growing number of second-line options relieves some of the concern when patients progress. Stadtmauer said he is now using BR more often in the second-line drug now that he is using BTK inhibitor more in the first line.

The Bcl-2 inhibitor venetoclax is highly effective and is another first- or second-line option even if this agent, like BTK inhibitors, also appears to require continuous dosing, said Stadtmauer, citing a study that showed patients relapsed relatively rapidly when the drug was stopped.

He now thinks of regimens with proteasome inhibitors as third line.

In selected patients who do not tolerate the non-covalent second-generation BTK inhibitors in the first or second line, he said, “I move quickly to the covalent BTKi pirtobrutinib,” based on data suggesting responses that are at least as good but with a better tolerability profile.
 

 

 

T-Cell Engager Data Are Limited

Without spending much time on the T-cell engagers, such as CAR T-cells or bispecific antibodies, Stadtmauer said that the advances he sees on the horizon “are tremendous,” and the “future is bright.” Such approaches could yield deep responses that could extend control or even provide cure, but these are speculations until more patients have been treated and followed long term.

Morton Coleman, MD, director of the Center for Lymphoma and Myeloma at Weill Cornell Medicine and the chairperson of the LLM Congress, called the talk a valuable and practical summary from a knowledgeable source. BTK inhibitors have represented a major evolution in WM management, but Coleman appreciated the underlying concept that treatment still has to be individualized.

“I think one of the most important take home messages is that the characterization of the mutational profile in patients with Waldenström should be considered a standard of care,” Coleman said. Helpful now, the mutational profile is likely to have a more valuable role as treatment is increasingly individualized.

Stadtmauer reported financial relationships with AbbVie, Bristol Myers Squibb, Celgene, Janssen, and Sorrento. Coleman disclosed ties with AbbVie, AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead, Loxo Oncology, Janssen, and Pharmacyclics.
 

A version of this article appeared on Medscape.com.

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A Dermatologist’s Tips for Supporting LGBTQ Youth

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Thu, 10/24/2024 - 15:06

Dermatologists who believe they have little to offer LGBTQ children and adolescents beyond routine care, Markus Boos, MD, PhD, urges them to consider the potential impact they can have on these patients.

“Sometimes in dermatology we might say, ‘This gender care stuff, that’s really for pediatricians and primary care doctors,’ ” Boos, a pediatric dermatologist at Seattle Children’s Hospital, Seattle, said at the annual meeting of the Pacific Dermatologic Association. However, he added, “gender-affirming care happens not only with medications but with communication, curiosity, and respect.” For instance, an LGBTQ patient who is being treated with isotretinoin for acne is seen once a month by a dermatologist, which is probably more frequent than seeing their primary care physician, he said. “Every time you see that child, you can make them feel seen. You can respect them. You can let them know that you care about them. Hopefully then they understand what it feels like to get good care from a provider and then will not settle for poor care from someone else.”

According to Gallup polling, the proportion of people in the United States who identify as non-cisgender or nonheterosexual increased from 3.5% in 2012 to 7% in 2021. “The estimation is that 2.5%-3.5% of all teenagers identify as gay or bisexual, and another 1% identify as transgender, though some studies estimate the percentage of gender diverse youth to be as high as 9.2%,” said Boos.

Dr. Boos
Dr. Markus Boos

He discussed several barriers to dermatologic care for LGBTQ youth, including availability. “There are only about 400 practicing pediatric dermatologists in the US, so there’s not a lot of pediatric dermatology care to go around for any child,” Boos said. “My plea to general dermatologists who see adolescents and teenagers: You can care for LGBTQ adolescents; they need your help.”

Accessibility is also an issue. For example, his clinic is in a wealthy and somewhat isolated area of Seattle, “which makes it hard for some patients to access our services because they may have to drive from far away or take multiple modes of public transportation to see us,” explained Boos, who came out as gay about 10 years ago after beginning his practice in Seattle. “Time matters, too. Children are in school. They don’t necessarily want to take time off to go to the doctor’s office. We want to make sure we have services at different times of day, including evenings or weekends if possible.”

Another potential barrier to care for this patient population is acceptability. “I can say that I welcome any patient to my practice, but if I’m not humble and informed about their concerns, especially queer or trans kids, if they feel that I’m not respecting them, that’s going to be a huge problem,” Boos said. “They won’t view that care as acceptable, and they’re not going to come back if they feel like I’m not looking out for their best interests.”

In a large cross-sectional study of patients with chronic inflammatory skin diseases published in 2023, sexual and gender minority (SGM) individuals were significantly more likely than non-SGM individuals to delay specialist care including dermatologic care (adjusted odds ratio [AOR], 1.23), mental health care (AOR, 1.62), and filing a prescription (AOR, 1.30) because of cost. The barriers for SGM patients were transportation issues, not having a healthcare practitioner (HCP) from the same racial or ethnic background, “and they were more likely to report not always being treated with respect by HCPs,” said Boos, who was not involved with the study. “SGM patients of minoritized racial identities such as Black, Hispanic, and Latino were also more likely to experience barriers to care.”

Boos offered several tips for improving the dermatologic care of LGBTQ youth:

Use inclusive language and follow your patient’s lead. “There are many ways that people identify, both with respect to their sexual orientation and their gender identity,” he said. “We often think that a person is either gay or straight, or cisgender or transgender. There are many folks who reject these binaries and may view their gender identity or sexual orientation outside of these descriptors. You can be bisexual. You can be asexual.” He also emphasized that sexual orientation is different from sexual behavior.

Be deliberate about your phrasing. Boos said he strives to make new patients feel comfortable by asking them such questions as what pronouns they use, how he should address them, and whether they have a partner or are in a relationship. “Then, in general, just follow your patient’s lead,” Boos said. “If they’re referring to their partner in a certain way or to themselves with certain pronouns, go along with it. When in doubt, just ask. And if you make a mistake like using the wrong pronouns or name of a patient, the best thing to do is immediately apologize and try your best not to repeat that error.”

When asking about sexual practices, don’t make assumptions. Boos recommends a 2019 article on dermatologic care of LGBT persons, published in the Journal of the American Academy of Dermatology, which includes specific examples of how to elicit a sexual history from adults and teens. One of the recommendations is “to be very direct, say, ‘This may feel uncomfortable, but I have to ask you these direct questions about what you’re doing sexually because I need to understand if you’re at risk for things like sexually transmitted infections,’ ” Boos said. “It’s also important to use terminology that our patients know. If I ask someone if they’ve had sex before, they usually understand that as penile-vaginal intercourse, but it’s also important to understand if they have oral or anal sex. But if you ask, ‘Have you had insertive anal sex?’ they may not know what that means as opposed to receptive anal sex. Instead, you might ask, ‘Are you a top or a bottom?’ which are more commonly used and understood terms in the queer community. It may feel really uncomfortable to use that kind of language, but we want to make sure patients understand what we’re asking them so we can take the best possible care of them.”

Pay attention to the details. One way to demonstrate inclusivity in your practice includes collecting pronoun and sexual orientation information for the electronic medical record so your entire staff can use proper pronouns for the patient. “Also, acknowledge that for queer folks, family can mean more than just biological family,” Boos added. “I do not buy into the stereotype that all queer kids are ostracized from their families and not loved by their families, but it is true that they are at risk for those experiences. So, sometimes a member of the patient’s ‘chosen family’ accompanies them on their visit.”

Privacy is also key. “You never know who else is in the room when you’re on a telehealth call, so you need to address that before you ask about personal things,” Boos said. “One sticking point that can also come up is that parents often fill out their child’s patient demographic form, which may not tell the real story. I typically start to have confidential time without parents and may take a sexual history as early as 12 or 13 years of age if it’s a patient that I’m seeing for an extended period or if I’m worried about a skin finding that might suggest an STI.”

He highlighted the unique opportunity dermatologists have to transform the healthcare landscape for LGBTQ children and adolescents. “It’s about extending yourself to nurture the growth of another person,” Boos said. “This can feel challenging, but you want to see each person for who they are and help get them to where they want to go. That’s what we went into medicine for, right? We want to care about people.”

Boos had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

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Dermatologists who believe they have little to offer LGBTQ children and adolescents beyond routine care, Markus Boos, MD, PhD, urges them to consider the potential impact they can have on these patients.

“Sometimes in dermatology we might say, ‘This gender care stuff, that’s really for pediatricians and primary care doctors,’ ” Boos, a pediatric dermatologist at Seattle Children’s Hospital, Seattle, said at the annual meeting of the Pacific Dermatologic Association. However, he added, “gender-affirming care happens not only with medications but with communication, curiosity, and respect.” For instance, an LGBTQ patient who is being treated with isotretinoin for acne is seen once a month by a dermatologist, which is probably more frequent than seeing their primary care physician, he said. “Every time you see that child, you can make them feel seen. You can respect them. You can let them know that you care about them. Hopefully then they understand what it feels like to get good care from a provider and then will not settle for poor care from someone else.”

According to Gallup polling, the proportion of people in the United States who identify as non-cisgender or nonheterosexual increased from 3.5% in 2012 to 7% in 2021. “The estimation is that 2.5%-3.5% of all teenagers identify as gay or bisexual, and another 1% identify as transgender, though some studies estimate the percentage of gender diverse youth to be as high as 9.2%,” said Boos.

Dr. Boos
Dr. Markus Boos

He discussed several barriers to dermatologic care for LGBTQ youth, including availability. “There are only about 400 practicing pediatric dermatologists in the US, so there’s not a lot of pediatric dermatology care to go around for any child,” Boos said. “My plea to general dermatologists who see adolescents and teenagers: You can care for LGBTQ adolescents; they need your help.”

Accessibility is also an issue. For example, his clinic is in a wealthy and somewhat isolated area of Seattle, “which makes it hard for some patients to access our services because they may have to drive from far away or take multiple modes of public transportation to see us,” explained Boos, who came out as gay about 10 years ago after beginning his practice in Seattle. “Time matters, too. Children are in school. They don’t necessarily want to take time off to go to the doctor’s office. We want to make sure we have services at different times of day, including evenings or weekends if possible.”

Another potential barrier to care for this patient population is acceptability. “I can say that I welcome any patient to my practice, but if I’m not humble and informed about their concerns, especially queer or trans kids, if they feel that I’m not respecting them, that’s going to be a huge problem,” Boos said. “They won’t view that care as acceptable, and they’re not going to come back if they feel like I’m not looking out for their best interests.”

In a large cross-sectional study of patients with chronic inflammatory skin diseases published in 2023, sexual and gender minority (SGM) individuals were significantly more likely than non-SGM individuals to delay specialist care including dermatologic care (adjusted odds ratio [AOR], 1.23), mental health care (AOR, 1.62), and filing a prescription (AOR, 1.30) because of cost. The barriers for SGM patients were transportation issues, not having a healthcare practitioner (HCP) from the same racial or ethnic background, “and they were more likely to report not always being treated with respect by HCPs,” said Boos, who was not involved with the study. “SGM patients of minoritized racial identities such as Black, Hispanic, and Latino were also more likely to experience barriers to care.”

Boos offered several tips for improving the dermatologic care of LGBTQ youth:

Use inclusive language and follow your patient’s lead. “There are many ways that people identify, both with respect to their sexual orientation and their gender identity,” he said. “We often think that a person is either gay or straight, or cisgender or transgender. There are many folks who reject these binaries and may view their gender identity or sexual orientation outside of these descriptors. You can be bisexual. You can be asexual.” He also emphasized that sexual orientation is different from sexual behavior.

Be deliberate about your phrasing. Boos said he strives to make new patients feel comfortable by asking them such questions as what pronouns they use, how he should address them, and whether they have a partner or are in a relationship. “Then, in general, just follow your patient’s lead,” Boos said. “If they’re referring to their partner in a certain way or to themselves with certain pronouns, go along with it. When in doubt, just ask. And if you make a mistake like using the wrong pronouns or name of a patient, the best thing to do is immediately apologize and try your best not to repeat that error.”

When asking about sexual practices, don’t make assumptions. Boos recommends a 2019 article on dermatologic care of LGBT persons, published in the Journal of the American Academy of Dermatology, which includes specific examples of how to elicit a sexual history from adults and teens. One of the recommendations is “to be very direct, say, ‘This may feel uncomfortable, but I have to ask you these direct questions about what you’re doing sexually because I need to understand if you’re at risk for things like sexually transmitted infections,’ ” Boos said. “It’s also important to use terminology that our patients know. If I ask someone if they’ve had sex before, they usually understand that as penile-vaginal intercourse, but it’s also important to understand if they have oral or anal sex. But if you ask, ‘Have you had insertive anal sex?’ they may not know what that means as opposed to receptive anal sex. Instead, you might ask, ‘Are you a top or a bottom?’ which are more commonly used and understood terms in the queer community. It may feel really uncomfortable to use that kind of language, but we want to make sure patients understand what we’re asking them so we can take the best possible care of them.”

Pay attention to the details. One way to demonstrate inclusivity in your practice includes collecting pronoun and sexual orientation information for the electronic medical record so your entire staff can use proper pronouns for the patient. “Also, acknowledge that for queer folks, family can mean more than just biological family,” Boos added. “I do not buy into the stereotype that all queer kids are ostracized from their families and not loved by their families, but it is true that they are at risk for those experiences. So, sometimes a member of the patient’s ‘chosen family’ accompanies them on their visit.”

Privacy is also key. “You never know who else is in the room when you’re on a telehealth call, so you need to address that before you ask about personal things,” Boos said. “One sticking point that can also come up is that parents often fill out their child’s patient demographic form, which may not tell the real story. I typically start to have confidential time without parents and may take a sexual history as early as 12 or 13 years of age if it’s a patient that I’m seeing for an extended period or if I’m worried about a skin finding that might suggest an STI.”

He highlighted the unique opportunity dermatologists have to transform the healthcare landscape for LGBTQ children and adolescents. “It’s about extending yourself to nurture the growth of another person,” Boos said. “This can feel challenging, but you want to see each person for who they are and help get them to where they want to go. That’s what we went into medicine for, right? We want to care about people.”

Boos had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

Dermatologists who believe they have little to offer LGBTQ children and adolescents beyond routine care, Markus Boos, MD, PhD, urges them to consider the potential impact they can have on these patients.

“Sometimes in dermatology we might say, ‘This gender care stuff, that’s really for pediatricians and primary care doctors,’ ” Boos, a pediatric dermatologist at Seattle Children’s Hospital, Seattle, said at the annual meeting of the Pacific Dermatologic Association. However, he added, “gender-affirming care happens not only with medications but with communication, curiosity, and respect.” For instance, an LGBTQ patient who is being treated with isotretinoin for acne is seen once a month by a dermatologist, which is probably more frequent than seeing their primary care physician, he said. “Every time you see that child, you can make them feel seen. You can respect them. You can let them know that you care about them. Hopefully then they understand what it feels like to get good care from a provider and then will not settle for poor care from someone else.”

According to Gallup polling, the proportion of people in the United States who identify as non-cisgender or nonheterosexual increased from 3.5% in 2012 to 7% in 2021. “The estimation is that 2.5%-3.5% of all teenagers identify as gay or bisexual, and another 1% identify as transgender, though some studies estimate the percentage of gender diverse youth to be as high as 9.2%,” said Boos.

Dr. Boos
Dr. Markus Boos

He discussed several barriers to dermatologic care for LGBTQ youth, including availability. “There are only about 400 practicing pediatric dermatologists in the US, so there’s not a lot of pediatric dermatology care to go around for any child,” Boos said. “My plea to general dermatologists who see adolescents and teenagers: You can care for LGBTQ adolescents; they need your help.”

Accessibility is also an issue. For example, his clinic is in a wealthy and somewhat isolated area of Seattle, “which makes it hard for some patients to access our services because they may have to drive from far away or take multiple modes of public transportation to see us,” explained Boos, who came out as gay about 10 years ago after beginning his practice in Seattle. “Time matters, too. Children are in school. They don’t necessarily want to take time off to go to the doctor’s office. We want to make sure we have services at different times of day, including evenings or weekends if possible.”

Another potential barrier to care for this patient population is acceptability. “I can say that I welcome any patient to my practice, but if I’m not humble and informed about their concerns, especially queer or trans kids, if they feel that I’m not respecting them, that’s going to be a huge problem,” Boos said. “They won’t view that care as acceptable, and they’re not going to come back if they feel like I’m not looking out for their best interests.”

In a large cross-sectional study of patients with chronic inflammatory skin diseases published in 2023, sexual and gender minority (SGM) individuals were significantly more likely than non-SGM individuals to delay specialist care including dermatologic care (adjusted odds ratio [AOR], 1.23), mental health care (AOR, 1.62), and filing a prescription (AOR, 1.30) because of cost. The barriers for SGM patients were transportation issues, not having a healthcare practitioner (HCP) from the same racial or ethnic background, “and they were more likely to report not always being treated with respect by HCPs,” said Boos, who was not involved with the study. “SGM patients of minoritized racial identities such as Black, Hispanic, and Latino were also more likely to experience barriers to care.”

Boos offered several tips for improving the dermatologic care of LGBTQ youth:

Use inclusive language and follow your patient’s lead. “There are many ways that people identify, both with respect to their sexual orientation and their gender identity,” he said. “We often think that a person is either gay or straight, or cisgender or transgender. There are many folks who reject these binaries and may view their gender identity or sexual orientation outside of these descriptors. You can be bisexual. You can be asexual.” He also emphasized that sexual orientation is different from sexual behavior.

Be deliberate about your phrasing. Boos said he strives to make new patients feel comfortable by asking them such questions as what pronouns they use, how he should address them, and whether they have a partner or are in a relationship. “Then, in general, just follow your patient’s lead,” Boos said. “If they’re referring to their partner in a certain way or to themselves with certain pronouns, go along with it. When in doubt, just ask. And if you make a mistake like using the wrong pronouns or name of a patient, the best thing to do is immediately apologize and try your best not to repeat that error.”

When asking about sexual practices, don’t make assumptions. Boos recommends a 2019 article on dermatologic care of LGBT persons, published in the Journal of the American Academy of Dermatology, which includes specific examples of how to elicit a sexual history from adults and teens. One of the recommendations is “to be very direct, say, ‘This may feel uncomfortable, but I have to ask you these direct questions about what you’re doing sexually because I need to understand if you’re at risk for things like sexually transmitted infections,’ ” Boos said. “It’s also important to use terminology that our patients know. If I ask someone if they’ve had sex before, they usually understand that as penile-vaginal intercourse, but it’s also important to understand if they have oral or anal sex. But if you ask, ‘Have you had insertive anal sex?’ they may not know what that means as opposed to receptive anal sex. Instead, you might ask, ‘Are you a top or a bottom?’ which are more commonly used and understood terms in the queer community. It may feel really uncomfortable to use that kind of language, but we want to make sure patients understand what we’re asking them so we can take the best possible care of them.”

Pay attention to the details. One way to demonstrate inclusivity in your practice includes collecting pronoun and sexual orientation information for the electronic medical record so your entire staff can use proper pronouns for the patient. “Also, acknowledge that for queer folks, family can mean more than just biological family,” Boos added. “I do not buy into the stereotype that all queer kids are ostracized from their families and not loved by their families, but it is true that they are at risk for those experiences. So, sometimes a member of the patient’s ‘chosen family’ accompanies them on their visit.”

Privacy is also key. “You never know who else is in the room when you’re on a telehealth call, so you need to address that before you ask about personal things,” Boos said. “One sticking point that can also come up is that parents often fill out their child’s patient demographic form, which may not tell the real story. I typically start to have confidential time without parents and may take a sexual history as early as 12 or 13 years of age if it’s a patient that I’m seeing for an extended period or if I’m worried about a skin finding that might suggest an STI.”

He highlighted the unique opportunity dermatologists have to transform the healthcare landscape for LGBTQ children and adolescents. “It’s about extending yourself to nurture the growth of another person,” Boos said. “This can feel challenging, but you want to see each person for who they are and help get them to where they want to go. That’s what we went into medicine for, right? We want to care about people.”

Boos had no relevant financial disclosures.
 

A version of this article appeared on Medscape.com.

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Remote Assessments: A Win-Win for ALS Patients and Clinics?

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Remote monitoring of respiratory scores in patients with amyotrophic lateral sclerosis (ALS) helps predict the best timing for the introduction of bilevel positive airway pressure (BiPAP), results of a retrospective study showed.

The findings, along with those of another study by the same group, suggest that remote monitoring of patients with ALS is a feasible option for both maximizing quality of life and minimizing cost and disruption.

Both studies were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

“What we’re trying to do is look for screening tools that we can use when these patients are in the community to see if a specific score transition is associated with a high probability of needing an intervention that would require bringing them in to do gold standard tests,” said study investigator Tefani Perera, MD, a neurology resident at the University of Calgary, in Alberta, Canada.
 

Optimizing Quality of Life

Tailoring in-person care is particularly important for patients with ALS who often face significant challenges with mobility, Perera said. However, most multidisciplinary ALS clinics schedule in-person follow-ups at regular intervals rather than “as needed.

“These are very long clinic days where they are assessed for one thing after another, even if they don’t need it. So maybe we can actually select for what they need to be assessed for at each specific visit? Life expectancy is not that long for these patients, so we want to make sure their quality of life is optimized.”

For the BiPAP study, the investigators used the Pooled Resource Open-Access ALS Clinical Trials database to identify patients with ALS with two or more respiratory assessments on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

The ALSFRS-R is a 12-item questionnaire, which includes three respiratory sub-scores for respiratory insufficiency (RiS), dyspnea (DyS) and orthopnea (OS).

Patients with a baseline RiS sub-score of 4 — meaning no need for BiPAP — were included in the study (n = 3838), with the primary outcome being a drop in RiS sub-score indicating the need for BiPAP.

The median time from baseline to transition to BiPAP was 563 days, with 3.4% of patients reaching this outcome by 3 months.

Results showed the probability of needing BiPAP was significantly associated with baseline DyS and OS scores (P < .0001). Among patients with baseline DyS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 5.5%, 8.7%, and 20.1%, respectively. In addition, in patients with baseline OS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 9.1%, 12.7%, and 24.2%, respectively.

Regardless of the baseline score, any drop in either of these sub-scores over the study period was also associated with an increased likelihood of requiring BiPAP within 3 months, with a DyS transition from 3 to 2 and an OS transition from 4 to 3 being most notable.

These scores could be used to trigger gold standard assessments for BiPAP, such as nocturnal oximetry, overnight polysomnography, daytime hypercapnia, and forced and slow vital capacities, Perera said. On the other hand, the scores could also help patients and clinicians avoid unnecessary visits.

“When the dyspnea and orthopnea scores are high, they might not need this intervention until 2 years later, so do we even need to bring them in to do these tests or see a respirologist when they don’t actually need it?”

The group’s second study was a systematic review of 26 papers on ALS remote assessment devices and methods, including accelerometers (15.4%), telenursing protocols (3.8%), speech collection apps (26.9%), questionnaires (15.4%), multifactorial sensors (15.4%), and respiratory function monitors (19.2%). Domains of symptoms monitored included speech (12 studies), motor (11 studies), respiratory (11 studies), cardiac (three studies), and bulbar, psychiatric, and autonomic (one study each).

The researchers characterized various remote tools as having potential and concluded that a multidomain approach to symptom monitoring is achievable. They also noted that the majority of studies assessing adherence and patient feedback indicated a favorable response to patient monitoring.

“I work in a resource-rich center, where we have these huge multidisciplinary clinics, and we have the capacity to bring patients back every 3 months, but outside these big centers, in resource-limited settings, to have an ability to track remotely and bring patients in when they really need it is very important,” said Perera.
 

 

 

Best of Both Worlds

Ileana Howard, MD, physiatrist and professor of rehabilitation medicine at the University of Washington and medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, agreed.

“One of the biggest challenges in ALS care today is ensuring equitable access to high quality care and supports, and telehealth was adopted by the VA early on as a means of doing that,” she said. “Remote monitoring technology is a really key development to help improve that type of care.”

However, she added that it should not be a question of one type of care versus the other. “The ideal care is when we have access to providing both face-to-face and virtual care for our patients so that we can meet their needs and preferences for care,” she said.

“Sometimes, in my experience, patients don’t understand why it’s important to go to an ALS specialty center. In those cases, I’ve been able to make initial contact with those individuals through telehealth and be able to provide education, which, in turn, often results in them making the decision to come to the specialty center once they understand what resources we have to offer.” 

Also commenting on the research, Ghazala Hayat, MD, also endorsed a mixed approach.

“Telehealth is a very good tool that we should use interspersed with in-person visits,” said Hayat, director of the multidisciplinary ALS clinic at St. Louis University School of Medicine, St. Louis, Missouri, and professor of neurology and director of neuromuscular and clinical neurophysiology.

“I think the first few visits should always be in person — you need to connect with the patient,” she said. “But then, once they feel comfortable, remote monitoring is a very good idea, especially later in the disease process, when it becomes really difficult for the family to bring the patient in.” 

The authors reported no relevant disclosures. Howard reported no disclosures. Hayat reported serving as a speaker and in advisory roles for argenx, Alexion, and MTPA. The study was funded by Amylyx Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

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Remote monitoring of respiratory scores in patients with amyotrophic lateral sclerosis (ALS) helps predict the best timing for the introduction of bilevel positive airway pressure (BiPAP), results of a retrospective study showed.

The findings, along with those of another study by the same group, suggest that remote monitoring of patients with ALS is a feasible option for both maximizing quality of life and minimizing cost and disruption.

Both studies were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

“What we’re trying to do is look for screening tools that we can use when these patients are in the community to see if a specific score transition is associated with a high probability of needing an intervention that would require bringing them in to do gold standard tests,” said study investigator Tefani Perera, MD, a neurology resident at the University of Calgary, in Alberta, Canada.
 

Optimizing Quality of Life

Tailoring in-person care is particularly important for patients with ALS who often face significant challenges with mobility, Perera said. However, most multidisciplinary ALS clinics schedule in-person follow-ups at regular intervals rather than “as needed.

“These are very long clinic days where they are assessed for one thing after another, even if they don’t need it. So maybe we can actually select for what they need to be assessed for at each specific visit? Life expectancy is not that long for these patients, so we want to make sure their quality of life is optimized.”

For the BiPAP study, the investigators used the Pooled Resource Open-Access ALS Clinical Trials database to identify patients with ALS with two or more respiratory assessments on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

The ALSFRS-R is a 12-item questionnaire, which includes three respiratory sub-scores for respiratory insufficiency (RiS), dyspnea (DyS) and orthopnea (OS).

Patients with a baseline RiS sub-score of 4 — meaning no need for BiPAP — were included in the study (n = 3838), with the primary outcome being a drop in RiS sub-score indicating the need for BiPAP.

The median time from baseline to transition to BiPAP was 563 days, with 3.4% of patients reaching this outcome by 3 months.

Results showed the probability of needing BiPAP was significantly associated with baseline DyS and OS scores (P < .0001). Among patients with baseline DyS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 5.5%, 8.7%, and 20.1%, respectively. In addition, in patients with baseline OS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 9.1%, 12.7%, and 24.2%, respectively.

Regardless of the baseline score, any drop in either of these sub-scores over the study period was also associated with an increased likelihood of requiring BiPAP within 3 months, with a DyS transition from 3 to 2 and an OS transition from 4 to 3 being most notable.

These scores could be used to trigger gold standard assessments for BiPAP, such as nocturnal oximetry, overnight polysomnography, daytime hypercapnia, and forced and slow vital capacities, Perera said. On the other hand, the scores could also help patients and clinicians avoid unnecessary visits.

“When the dyspnea and orthopnea scores are high, they might not need this intervention until 2 years later, so do we even need to bring them in to do these tests or see a respirologist when they don’t actually need it?”

The group’s second study was a systematic review of 26 papers on ALS remote assessment devices and methods, including accelerometers (15.4%), telenursing protocols (3.8%), speech collection apps (26.9%), questionnaires (15.4%), multifactorial sensors (15.4%), and respiratory function monitors (19.2%). Domains of symptoms monitored included speech (12 studies), motor (11 studies), respiratory (11 studies), cardiac (three studies), and bulbar, psychiatric, and autonomic (one study each).

The researchers characterized various remote tools as having potential and concluded that a multidomain approach to symptom monitoring is achievable. They also noted that the majority of studies assessing adherence and patient feedback indicated a favorable response to patient monitoring.

“I work in a resource-rich center, where we have these huge multidisciplinary clinics, and we have the capacity to bring patients back every 3 months, but outside these big centers, in resource-limited settings, to have an ability to track remotely and bring patients in when they really need it is very important,” said Perera.
 

 

 

Best of Both Worlds

Ileana Howard, MD, physiatrist and professor of rehabilitation medicine at the University of Washington and medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, agreed.

“One of the biggest challenges in ALS care today is ensuring equitable access to high quality care and supports, and telehealth was adopted by the VA early on as a means of doing that,” she said. “Remote monitoring technology is a really key development to help improve that type of care.”

However, she added that it should not be a question of one type of care versus the other. “The ideal care is when we have access to providing both face-to-face and virtual care for our patients so that we can meet their needs and preferences for care,” she said.

“Sometimes, in my experience, patients don’t understand why it’s important to go to an ALS specialty center. In those cases, I’ve been able to make initial contact with those individuals through telehealth and be able to provide education, which, in turn, often results in them making the decision to come to the specialty center once they understand what resources we have to offer.” 

Also commenting on the research, Ghazala Hayat, MD, also endorsed a mixed approach.

“Telehealth is a very good tool that we should use interspersed with in-person visits,” said Hayat, director of the multidisciplinary ALS clinic at St. Louis University School of Medicine, St. Louis, Missouri, and professor of neurology and director of neuromuscular and clinical neurophysiology.

“I think the first few visits should always be in person — you need to connect with the patient,” she said. “But then, once they feel comfortable, remote monitoring is a very good idea, especially later in the disease process, when it becomes really difficult for the family to bring the patient in.” 

The authors reported no relevant disclosures. Howard reported no disclosures. Hayat reported serving as a speaker and in advisory roles for argenx, Alexion, and MTPA. The study was funded by Amylyx Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

Remote monitoring of respiratory scores in patients with amyotrophic lateral sclerosis (ALS) helps predict the best timing for the introduction of bilevel positive airway pressure (BiPAP), results of a retrospective study showed.

The findings, along with those of another study by the same group, suggest that remote monitoring of patients with ALS is a feasible option for both maximizing quality of life and minimizing cost and disruption.

Both studies were presented at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.

“What we’re trying to do is look for screening tools that we can use when these patients are in the community to see if a specific score transition is associated with a high probability of needing an intervention that would require bringing them in to do gold standard tests,” said study investigator Tefani Perera, MD, a neurology resident at the University of Calgary, in Alberta, Canada.
 

Optimizing Quality of Life

Tailoring in-person care is particularly important for patients with ALS who often face significant challenges with mobility, Perera said. However, most multidisciplinary ALS clinics schedule in-person follow-ups at regular intervals rather than “as needed.

“These are very long clinic days where they are assessed for one thing after another, even if they don’t need it. So maybe we can actually select for what they need to be assessed for at each specific visit? Life expectancy is not that long for these patients, so we want to make sure their quality of life is optimized.”

For the BiPAP study, the investigators used the Pooled Resource Open-Access ALS Clinical Trials database to identify patients with ALS with two or more respiratory assessments on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

The ALSFRS-R is a 12-item questionnaire, which includes three respiratory sub-scores for respiratory insufficiency (RiS), dyspnea (DyS) and orthopnea (OS).

Patients with a baseline RiS sub-score of 4 — meaning no need for BiPAP — were included in the study (n = 3838), with the primary outcome being a drop in RiS sub-score indicating the need for BiPAP.

The median time from baseline to transition to BiPAP was 563 days, with 3.4% of patients reaching this outcome by 3 months.

Results showed the probability of needing BiPAP was significantly associated with baseline DyS and OS scores (P < .0001). Among patients with baseline DyS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 5.5%, 8.7%, and 20.1%, respectively. In addition, in patients with baseline OS scores of 3, 2, and 1, the percentages of patients needing BiPAP within 3 months were 9.1%, 12.7%, and 24.2%, respectively.

Regardless of the baseline score, any drop in either of these sub-scores over the study period was also associated with an increased likelihood of requiring BiPAP within 3 months, with a DyS transition from 3 to 2 and an OS transition from 4 to 3 being most notable.

These scores could be used to trigger gold standard assessments for BiPAP, such as nocturnal oximetry, overnight polysomnography, daytime hypercapnia, and forced and slow vital capacities, Perera said. On the other hand, the scores could also help patients and clinicians avoid unnecessary visits.

“When the dyspnea and orthopnea scores are high, they might not need this intervention until 2 years later, so do we even need to bring them in to do these tests or see a respirologist when they don’t actually need it?”

The group’s second study was a systematic review of 26 papers on ALS remote assessment devices and methods, including accelerometers (15.4%), telenursing protocols (3.8%), speech collection apps (26.9%), questionnaires (15.4%), multifactorial sensors (15.4%), and respiratory function monitors (19.2%). Domains of symptoms monitored included speech (12 studies), motor (11 studies), respiratory (11 studies), cardiac (three studies), and bulbar, psychiatric, and autonomic (one study each).

The researchers characterized various remote tools as having potential and concluded that a multidomain approach to symptom monitoring is achievable. They also noted that the majority of studies assessing adherence and patient feedback indicated a favorable response to patient monitoring.

“I work in a resource-rich center, where we have these huge multidisciplinary clinics, and we have the capacity to bring patients back every 3 months, but outside these big centers, in resource-limited settings, to have an ability to track remotely and bring patients in when they really need it is very important,” said Perera.
 

 

 

Best of Both Worlds

Ileana Howard, MD, physiatrist and professor of rehabilitation medicine at the University of Washington and medical co-director of the ALS Center of Excellence at VA Puget Sound in Seattle, agreed.

“One of the biggest challenges in ALS care today is ensuring equitable access to high quality care and supports, and telehealth was adopted by the VA early on as a means of doing that,” she said. “Remote monitoring technology is a really key development to help improve that type of care.”

However, she added that it should not be a question of one type of care versus the other. “The ideal care is when we have access to providing both face-to-face and virtual care for our patients so that we can meet their needs and preferences for care,” she said.

“Sometimes, in my experience, patients don’t understand why it’s important to go to an ALS specialty center. In those cases, I’ve been able to make initial contact with those individuals through telehealth and be able to provide education, which, in turn, often results in them making the decision to come to the specialty center once they understand what resources we have to offer.” 

Also commenting on the research, Ghazala Hayat, MD, also endorsed a mixed approach.

“Telehealth is a very good tool that we should use interspersed with in-person visits,” said Hayat, director of the multidisciplinary ALS clinic at St. Louis University School of Medicine, St. Louis, Missouri, and professor of neurology and director of neuromuscular and clinical neurophysiology.

“I think the first few visits should always be in person — you need to connect with the patient,” she said. “But then, once they feel comfortable, remote monitoring is a very good idea, especially later in the disease process, when it becomes really difficult for the family to bring the patient in.” 

The authors reported no relevant disclosures. Howard reported no disclosures. Hayat reported serving as a speaker and in advisory roles for argenx, Alexion, and MTPA. The study was funded by Amylyx Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

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Cannabis in Cancer: What Oncologists and Patients Should Know

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Wed, 11/06/2024 - 05:20

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

 

 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

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Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

 

 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

Many patients use cannabis to manage their cancer-related symptoms. However, research indicates that patients often do so without speaking to their oncologists first, and oncologists may be hesitant to broach the topic with their patients.

Updated guidelines from the American Society of Clinical Oncology (ASCO) on the use of cannabis and cannabinoids in adults with cancer stress that it’s an important conversation to have.

According to the ASCO expert panel, access to and use of cannabis alongside cancer care have outpaced the science on evidence-based indications, and overall high-quality data on the effects of cannabis during cancer care are lacking. While several observational studies support cannabis use to help ease chemotherapy-related nausea and vomiting, the literature remains more divided on other potential benefits, such as alleviating cancer pain and sleep problems, and some evidence points to potential downsides of cannabis use.

Oncologists should “absolutely talk to patients” about cannabis, Brooke Worster, MD, medical director for the Master of Science in Medical Cannabis Science & Business program at Thomas Jefferson University, Philadelphia, told Medscape Medical News.

“Patients are interested, and they are going to find access to information. As a medical professional, it’s our job to help guide them through these spaces in a safe, nonjudgmental way.”

But, Worster noted, oncologists don’t have to be experts on cannabis to begin the conversation with patients.

So, “let yourself off the hook,” Worster urged.

Plus, avoiding the conversation won’t stop patients from using cannabis. In a recent study, Worster and her colleagues found that nearly one third of patients at 12 National Cancer Institute-designated cancer centers had used cannabis since their diagnosis — most often for sleep disturbance, pain, stress, and anxiety. Most (60%) felt somewhat or extremely comfortable talking to their healthcare provider about it, but only 21.5% said they had done so. Even fewer — about 10% — had talked to their treating oncologist.

Because patients may not discuss cannabis use, it’s especially important for oncologists to open up a line of communication, said Worster, also the enterprise director of supportive oncology at the Thomas Jefferson University.
 

Evidence on Cannabis During Cancer Care

A substantial proportion of people with cancer believe cannabis can help manage cancer-related symptoms.

In Worster’s recent survey study, regardless of whether patients had used cannabis, almost 90% of those surveyed reported a perceived benefit. Although 65% also reported perceived risks for cannabis use, including difficulty concentrating, lung damage, and impaired memory, the perceived benefits outweighed the risks.

Despite generally positive perceptions, the overall literature on the benefits of cannabis in patients with cancer paints a less clear picture.

The ASCO guidelines, which were based on 13 systematic reviews and five additional primary studies, reported that cannabis can improve refractory, chemotherapy-induced nausea or vomiting when added to guideline-concordant antiemetic regimens, but that there is no clear evidence of benefit or harm for other supportive care outcomes.

The “certainty of evidence for most outcomes was low or very low,” the ASCO authors wrote.

The ASCO experts explained that, outside the context of a clinical trial, the evidence is not sufficient to recommend cannabis or cannabinoids for managing cancer pain, sleep issues, appetite loss, or anxiety and depression. For these outcomes, some studies indicate a benefit, while others don’t.

Real-world data from a large registry study, for instance, have indicated that medical cannabis is “a safe and effective complementary treatment for pain relief in patients with cancer.” However, a 2020 meta-analysis found that, in studies with a low risk for bias, adding cannabinoids to opioids did not reduce cancer pain in adults with advanced cancer.

There can be downsides to cannabis use, too. In one recent study, some patients reported feeling worse physically and psychologically compared with those who didn’t use cannabis. Another study found that oral cannabis was associated with “bothersome” side effects, including sedation, dizziness, and transient anxiety.

The ASCO guidelines also made it clear that cannabis or cannabinoids should not be used as cancer-directed treatment, outside of a clinical trial.
 

 

 

Talking to Patients About Cannabis

Given the level of evidence and patient interest in cannabis, it is important for oncologists to raise the topic of cannabis use with their patients.

To help inform decision-making and approaches to care, the ASCO guidelines suggest that oncologists can guide care themselves or direct patients to appropriate “unbiased, evidence-based” resources. For those who use cannabis or cannabinoids outside of evidence-based indications or clinician recommendations, it’s important to explore patients’ goals, educate them, and try to minimize harm.

One strategy for broaching the topic, Worster suggested, is to simply ask patients if they have tried or considered trying cannabis to control symptoms like nausea and vomiting, loss of appetite, or cancer pain.

The conversation with patients should then include an overview of the potential benefits and potential risks for cannabis use as well as risk reduction strategies, Worster noted.

But “approach it in an open and nonjudgmental frame of mind,” she said. “Just have a conversation.”

Discussing the formulation and concentration of tetrahydrocannabinol (THC) and cannabidiol (CBD) in products matters as well.

Will the product be inhaled, ingested, or topical? Inhaled cannabis is not ideal but is sometimes what patients have access to, Worster explained. Inhaled formulations tend to have faster onset, which might be preferable for treating chemotherapy-related nausea and vomiting, whereas edible formulations may take a while to start working.

It’s also important to warn patients about taking too much, she said, explaining that inhaling THC at higher doses can increase the risk for cardiovascular effects, anxiety, paranoia, panic, and psychosis.

CBD, on the other hand, is anti-inflammatory, but early data suggest it may blunt immune responses in high doses and should be used cautiously by patients receiving immunotherapy.

Worster noted that as laws change and the science advances, new cannabis products and formulations will emerge, as will artificial intelligence tools for helping to guide patients and clinicians in optimal use of cannabis for cancer care. State websites are a particularly helpful tool for providing state-specific medical education related to cannabis laws and use, as well, she said.

The bottom line, she said, is that talking to patients about the ins and outs of cannabis use “really matters.”

Worster disclosed that she is a medical consultant for EO Care.
 

A version of this article appeared on Medscape.com.

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