Video

WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.

Vidyard Video

“Part of planning for surgery is to prevent that sort of problem,” and fortunately, when sutures and pressure don’t do the trick for excess bleeding, there are several hemostatic products that can be used, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.

SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.

Vidyard Video

“Part of planning for surgery is to prevent that sort of problem,” and fortunately, when sutures and pressure don’t do the trick for excess bleeding, there are several hemostatic products that can be used, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.

SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – “Nothing can ruin your day more than a lot of bleeding,” said Mohs surgeon Daniel Siegel, MD, clinical professor of dermatology at the State University of New York Downstate Medical Center, New York.

Vidyard Video

“Part of planning for surgery is to prevent that sort of problem,” and fortunately, when sutures and pressure don’t do the trick for excess bleeding, there are several hemostatic products that can be used, and some are very inexpensive. There’s even a “fancy form of potato starch” that can be left in the wound and sewn over, he said in an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation.

During the interview, Dr. Siegel described several options and how to use them. They are good products to have on hand in the clinic, just in case, he said.

SDEF/Global Academy for Medical Education and this news organization and are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – Since its approval in 2017, dupilumab (Dupixent) has proven to be a solid addition to the atopic dermatitis (AD) armamentarium.

Vidyard Video

About 80% to 85% of patients treated with the biologic will achieve a 50% reduction in their Eczema Area and Severity Index score, and some will go on to a 90% reduction, according to Jonathan Silverberg, MD, PhD, of the department of dermatology, Northwestern University, Chicago.

But one side effect associated with dupilumab has been vexing to dermatologists: conjunctivitis in 15% or so of patients. Dr. Silverberg has seen it in his own practice and said it can be hard to know whether or not to refer to ophthalmology. “We’re often left with this conundrum of ... ‘Is it a side effect of the medication, or is it just because they happen to have hay fever or keratoconjunctivitis or other ophthalmic comorbidities?’ And it’s not always easy to sort out.”


In an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation, he offered his advice on managing a patient who develops conjunctivitis during dupilumab treatment, including his treatment tips for when it is safe to handle in the dermatology clinic.

Dr. Silverberg, who was an investigator in the dupilumab phase 3 trials, said that, while dupilumab is the only systemic agent approved by the Food and Drug Administration for treating AD, and more are on the way for AD, there will always still be a role for traditional immunosuppressives. He explained why in the interview and why he favors methotrexate when old school options are in order.

This news organization and SDEF/Global Academy for Medical Education are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Since its approval in 2017, dupilumab (Dupixent) has proven to be a solid addition to the atopic dermatitis (AD) armamentarium.

Vidyard Video

About 80% to 85% of patients treated with the biologic will achieve a 50% reduction in their Eczema Area and Severity Index score, and some will go on to a 90% reduction, according to Jonathan Silverberg, MD, PhD, of the department of dermatology, Northwestern University, Chicago.

But one side effect associated with dupilumab has been vexing to dermatologists: conjunctivitis in 15% or so of patients. Dr. Silverberg has seen it in his own practice and said it can be hard to know whether or not to refer to ophthalmology. “We’re often left with this conundrum of ... ‘Is it a side effect of the medication, or is it just because they happen to have hay fever or keratoconjunctivitis or other ophthalmic comorbidities?’ And it’s not always easy to sort out.”


In an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation, he offered his advice on managing a patient who develops conjunctivitis during dupilumab treatment, including his treatment tips for when it is safe to handle in the dermatology clinic.

Dr. Silverberg, who was an investigator in the dupilumab phase 3 trials, said that, while dupilumab is the only systemic agent approved by the Food and Drug Administration for treating AD, and more are on the way for AD, there will always still be a role for traditional immunosuppressives. He explained why in the interview and why he favors methotrexate when old school options are in order.

This news organization and SDEF/Global Academy for Medical Education are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – Since its approval in 2017, dupilumab (Dupixent) has proven to be a solid addition to the atopic dermatitis (AD) armamentarium.

Vidyard Video

About 80% to 85% of patients treated with the biologic will achieve a 50% reduction in their Eczema Area and Severity Index score, and some will go on to a 90% reduction, according to Jonathan Silverberg, MD, PhD, of the department of dermatology, Northwestern University, Chicago.

But one side effect associated with dupilumab has been vexing to dermatologists: conjunctivitis in 15% or so of patients. Dr. Silverberg has seen it in his own practice and said it can be hard to know whether or not to refer to ophthalmology. “We’re often left with this conundrum of ... ‘Is it a side effect of the medication, or is it just because they happen to have hay fever or keratoconjunctivitis or other ophthalmic comorbidities?’ And it’s not always easy to sort out.”


In an interview at the Hawaii Dermatology Seminar, provided by Global Academy for Medical Education/Skin Disease Education Foundation, he offered his advice on managing a patient who develops conjunctivitis during dupilumab treatment, including his treatment tips for when it is safe to handle in the dermatology clinic.

Dr. Silverberg, who was an investigator in the dupilumab phase 3 trials, said that, while dupilumab is the only systemic agent approved by the Food and Drug Administration for treating AD, and more are on the way for AD, there will always still be a role for traditional immunosuppressives. He explained why in the interview and why he favors methotrexate when old school options are in order.

This news organization and SDEF/Global Academy for Medical Education are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The work up of a case of onychomycosis doesn’t end with the detection of fungal hyphae.

Trichophyton rubrum remains the most common cause of toenail fungus in the United States, but nondermatophyte molds – Scopulariopsis, Fusarium, and others – are on the rise, so it’s important to speciate, especially when patients have atypical presentations or fail to respond to the T. rubrum go-to treatment, terbinafine, according to Nathaniel Jellinek, MD, of the department of dermatology, Brown University, Providence, R.I.

Standard in-office potassium hydroxide (KOH) testing can’t distinguish one species of fungus from another, nor can pathology with Gomori methenamine silver (GMS) or Periodic acid-Schiff (PAS) staining. Both culture and polymerase chain reaction (PCR), however, do.

Since few hospitals are equipped to run those tests, Dr. Jellinek uses the Case Western Center for Medical Mycology, in Cleveland, for testing.

In an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Jellinek explained how to speciate, and the importance of doing so.

He also shared his tips on getting good nail clippings and good scrapings for debris for testing, and explained when KOH testing is enough – and when to opt for more advanced diagnostic methods, including PCR, which he said trumps all previous methods.

Terbinafine is still the best option for T. rubrum, but new topicals are better for nondermatophyte molds. There’s also a clever new dosing regimen for terbinafine, one that should put patients at ease about liver toxicity and other concerns. “If you tell them they’re getting 1 month off in the middle, it seems to go over a little easier,” Dr. Jellinek said.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – The work up of a case of onychomycosis doesn’t end with the detection of fungal hyphae.

Trichophyton rubrum remains the most common cause of toenail fungus in the United States, but nondermatophyte molds – Scopulariopsis, Fusarium, and others – are on the rise, so it’s important to speciate, especially when patients have atypical presentations or fail to respond to the T. rubrum go-to treatment, terbinafine, according to Nathaniel Jellinek, MD, of the department of dermatology, Brown University, Providence, R.I.

Standard in-office potassium hydroxide (KOH) testing can’t distinguish one species of fungus from another, nor can pathology with Gomori methenamine silver (GMS) or Periodic acid-Schiff (PAS) staining. Both culture and polymerase chain reaction (PCR), however, do.

Since few hospitals are equipped to run those tests, Dr. Jellinek uses the Case Western Center for Medical Mycology, in Cleveland, for testing.

In an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Jellinek explained how to speciate, and the importance of doing so.

He also shared his tips on getting good nail clippings and good scrapings for debris for testing, and explained when KOH testing is enough – and when to opt for more advanced diagnostic methods, including PCR, which he said trumps all previous methods.

Terbinafine is still the best option for T. rubrum, but new topicals are better for nondermatophyte molds. There’s also a clever new dosing regimen for terbinafine, one that should put patients at ease about liver toxicity and other concerns. “If you tell them they’re getting 1 month off in the middle, it seems to go over a little easier,” Dr. Jellinek said.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – The work up of a case of onychomycosis doesn’t end with the detection of fungal hyphae.

Trichophyton rubrum remains the most common cause of toenail fungus in the United States, but nondermatophyte molds – Scopulariopsis, Fusarium, and others – are on the rise, so it’s important to speciate, especially when patients have atypical presentations or fail to respond to the T. rubrum go-to treatment, terbinafine, according to Nathaniel Jellinek, MD, of the department of dermatology, Brown University, Providence, R.I.

Standard in-office potassium hydroxide (KOH) testing can’t distinguish one species of fungus from another, nor can pathology with Gomori methenamine silver (GMS) or Periodic acid-Schiff (PAS) staining. Both culture and polymerase chain reaction (PCR), however, do.

Since few hospitals are equipped to run those tests, Dr. Jellinek uses the Case Western Center for Medical Mycology, in Cleveland, for testing.

In an interview at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Jellinek explained how to speciate, and the importance of doing so.

He also shared his tips on getting good nail clippings and good scrapings for debris for testing, and explained when KOH testing is enough – and when to opt for more advanced diagnostic methods, including PCR, which he said trumps all previous methods.

Terbinafine is still the best option for T. rubrum, but new topicals are better for nondermatophyte molds. There’s also a clever new dosing regimen for terbinafine, one that should put patients at ease about liver toxicity and other concerns. “If you tell them they’re getting 1 month off in the middle, it seems to go over a little easier,” Dr. Jellinek said.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – The best way to approach a patient with rosacea is to look at the individual symptoms, according to Linda Stein Gold, MD, director of dermatology research at Henry Ford Hospital in Detroit.

Vidyard Video

Papules and pustules need an oral or topical anti-inflammatory drug. Background erythema requires an alpha adrenergic agonist. Telangiectasia is best handled by a laser device, and if a patient has a phyma, “you’ve got to use a surgical approach,” she said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. It sounds simple, but there are decisions to be made about what drugs and formulations to use, and when, and when to combine them.

In an interview, Dr. Stein Gold shared her approach to treatment, along with the latest on using ivermectin and brimonidine together, plus her thoughts on new medications under development and the role of the Demodex mite in rosacea.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

WAIKOLOA, HAWAII – There’s really not much reason to shy away from isotretinoin, spironolactone, and oral contraceptives for acne, according to Julie Harper, MD, of the department of dermatology at the University of Alabama at Birmingham.

There have been concerns with all three in the past, but most of the worries have been recently laid to rest.

The news hasn’t reached everyone, though, so, by and large, they are “tools I think we are not using enough of,” Dr. Harper said in an interview. With isotretinoin, for instance, it really isn’t necessary to do blood work for lipids and liver function every month, a daunting prospect for patients; baseline testing with a repeat at 2 months is sufficient, as long as there’s no dose escalation and results are acceptable, with the exception of a monthly pregnancy test for women, she noted. Meanwhile, there’s no evidence of a link with inflammatory bowel disease, and wound healing isn’t as much of an issue as once thought.

It’s the same story with spironolactone. Hyperkalemia is a long-standing concern, but it turns out that “in healthy young women taking spironolactone for acne, we don’t need to be checking potassium.” As far as breast cancer goes, the potential risk with spironolactone hasn’t panned out in the literature, and there may not be “a link at all,” Dr. Harper said at the Hawaii Dermatology Seminar provided by the Global Academy for Medical Education/Skin Disease Education Foundation.

There are caveats, of course. Hormonal treatments shouldn’t be used in young women until they’ve established their menstrual cycle. OCs should not be used in smokers, or people who have hypertension or migraines, among other conditions. Also, elevated triglycerides remain a concern with isotretinoin. “The number I would want people to remember is 500 [mg/dL],” the threshold when triglycerides become a problem.

In the interview, Dr. Harper explained the new thinking on these three options, and shared her treatment tips, including what to do if patients’ triglycerides hit the 500 mg/dL mark.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

HONOLULU – A minimally invasive approach to lysing an intracerebral hemorrhage clot was safe but failed to produce a statistically significant improvement in long-term functional outcome when compared with usual medical management in a phase 3 randomized trial of 499 patients. However, the results also showed that when the procedure met its acute goal of cutting residual clot to a volume of 15 mL or less, it significantly boosted the percentage of patients with a modified Rankin Scale score of 0-3 when assessed a year after treatment, Daniel F. Hanley Jr., MD, said at the International Stroke Conference, sponsored by the American Heart Association.

“Improved function and increased survival was produced by surgical [clot] reduction to 15 mL or less,” said Dr. Hanley, professor of neurology at Johns Hopkins University, Baltimore, and one of the organizers of the MISTIE III trial.

When assessed by another measure, treated patients showed significant, long-term functional improvement compared with controls when their clot burden dropped by at least 70% following the lytic procedure.

“This is the first description of specific thresholds of hematoma evacuation that impact functional outcomes in intracerebral hemorrhage surgery trials,” said Issam A. Awad, MD, professor of surgery and director of neurovascular surgery at the University of Chicago and coprincipal investigator of the trial.

The problem in the trial was that the surgeons who performed the interventions did not treat many patients aggressively enough to reach these thresholds. They achieved the prespecified goal of residual clot of 15 mL or less in 59% of patients, Dr. Hanley reported, even though the study protocol called for serial infusions of 1 mg of tissue plasminogen activator (Alteplase) into the clot via a placed catheter as many as nine times, administered at 8 hour intervals, with treatment to continue until patients reached the goal residual volume or until they had received all nine doses. In actual practice during the study, operators administered a median of four lytic doses.

“We showed that this goal was important, but not all sites embraced the goal,” Dr. Hanley said. Even though the participating clinicians had a specific interest in intracerebral hemorrhage patients and in this procedure, several nonetheless “had a poor understanding of the goal,” he said in an interview. He attributed the less-than-aggressive approach many operators took to the safety concern that further doses of the lytic drug could trigger recurrent hemorrhage.

“We showed that the goal was important. I think they will embrace the [hematoma evacuation] goal when they see these data,” Dr. Hanley predicted.

An as-treated analysis of the data that focused on the 145 of 246 patients who were treated with minimally invasive lysis and reached the target residual volume and who were then functionally assessed a year later, showed that the rate of patients with a modified Rankin Scale score of 0-3 was 53%, compared with 42% among the controls, an 11% difference.

This shows “a large treatment effect. This is a big, transformative treatment,” Dr. Hanley said. “Our data clearly show that more than half the patients had a positive outcome when their surgeons were more aggressive about clot removal.” He cautioned that the trial was not just about the volume of clot removed but was also about doing it in a gentle way, with a minimum of tissue trauma. Other approaches to reducing hematoma volume may be faster or more complete but they cannot now match the record of safety and efficacy documented in MISTIE III for minimally invasive clot lysis, Dr. Hanley noted.

MISTIE III (Minimally Invasive Surgery Plus Rt-PA for ICH Evacuation Phase III) enrolled patients at 78 centers in the United States and several other countries during 2013-2017. Patients had to enroll 12-72 hours after onset and present with a hematoma volume of at least 30 mL. Participating neurosurgeons used image-guided neuronavigation to place a 4- to 6-mm cannula through the clot, ideally straight through the hematoma’s long axis and with the tip placed within the largest clot segment. Among the 110 surgeons who performed this procedure during the study, 88% had never done it before, and operator and site experience linked with better performance. No surgeon who had already performed four minimally invasive lytic cases, and no center that had already performed seven cases, had a subsequent patient with a residual volume that exceeded 30 mL, Dr. Awad said. The surgical experience during the trial showed that catheter repositioning and using a second catheter were both safe ways to maximize evacuation of the hematoma, he added.

The trial’s primary endpoint, the rate of patients with a modified Rankin Scale score of 0-3 at 1 year after treatment in a modified intention-to-treat analysis that included all patients regardless of the amount of hematoma evacuation they received, showed a 45% rate among the patients who underwent minimally invasive lysis and a 41% rate among those in the control arm, a difference that was not statistically significant. Safety assessments showed that patients treated with the investigational approach had significantly lower mortality 7 days after treatment: 0.8% compared with 4.0%. By 1 year after treatment, mortality was cut by one-third in the minimally invasive patients, compared with the control patients, also a statistically significant difference. The rates of symptomatic bleeds and brain infections were similar in the two treatment groups, Dr. Hanley reported. Concurrently with his talk at the conference, a paper with the primary study results appeared online (Lancet. 2019 Feb 7. doi: 10.1016/S0140-6736[19]30195-3).

MISTIE III was supported by the National Institute of Neurological Disorders and Stroke. The trial received no commercial support aside from free tissue plasminogen activator (Alteplase) supplied by Genentech. Dr. Hanley has been a consultant to BrainScope, Neurotrope, Portola, and Op2Lysis, and he has served as an expert witness on behalf of Medtronic. Dr. Awad had no disclosures.

[email protected]

SOURCE: Hanley DF et al. ISC 2019, Abstract LB4; Awad IS et al. ISC 2019, Abstract LB5.

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

Eight weeks of a mindfulness intervention known as acceptance and commitment therapy (ACT) significantly improved stress and depression among patients with inflammatory bowel disease, and these improvements persisted for at least 12 weeks after therapy ended, according to the results of a randomized, controlled trial.

Source: The American Gastroenterological Association

In the intention-to-treat analysis, stress symptoms, as measured by the Depression Anxiety and Stress Scales (DASS-21), improved by 39% at week 8 and by 45% at week 20, reported Brona Wynne, PhD, of University College Dublin together with her associates. These improvements were highly significant compared with baseline and treatment as usual (P = .001 for both comparisons). “Post hoc analyses indicated that baseline stress levels were similar in control and treatment groups,” the researchers wrote in Gastroenterology. “The results of the per protocol analysis were comparable, with a 43% and 49% reduction in stress in the treatment group from baseline to 8 and 20 weeks.”

Multiple studies have documented high levels of stress and psychological dysfunction among patients with Crohn’s disease and ulcerative colitis. Studies of various mindfulness therapy, relaxation, stress management, cognitive-behavioral therapy, and hypnotherapy interventions often failed to collect key clinical data or were underpowered, uncontrolled, and unrandomized. Acceptance and commitment therapy uses mindfulness to identify adverse thoughts and experiences, accept these as part of life, and recommit to “move towards values that have been identified and adopted by the individual,” the investigators wrote. “This can be defined as the ability to contact the present moment more fully as a conscious human being and to change, or persist in, behavior when doing so serves valued ends.”

Their single-center study, which they said was the first to evaluate ACT in IBD patients, included 79 individuals with stable or mildly active Crohn’s disease (38 patients) or ulcerative colitis (41 patients) who were randomly assigned to ACT (37 patients) or control treatment as usual (42 patients). The two comparison groups were demographically and clinically similar. The ACT program involved eight 90-minute, weekly sessions of groups of 14-16 individuals, led by a single psychologist who tailored the course material toward IBD with a focus on lowering stress. An independent psychologist observed each session to assess adherence to protocol.

Not only did ACT meet the primary study endpoint, it also produced a 25% decrease in perceived stress (on a 1-10 scale) by week 8 and a 27% decrease in perceived stress by week 20 (P less than .001 versus treatment as usual). Depression scores in the ACT group also fell by 47% by week 8 and by 45% at week 20 (P = .01 versus treatment as usual). Anxiety levels decreased by 29% at week 8 and by 31% at week 20, but these improvements did not significantly differ from those in the control group (P = .39).

Interestingly, ACT did not significantly improve symptom burden, activities of daily living, disease-related worry, general well-being, C-reactive protein (CRP) levels, fecal calprotectin levels, or scores on the version used of the Clinical Assessment of Depression (CAD) or the short Mayo assessment. Hair cortisol levels showed an association with baseline stress and anxiety, but not with treatment response.

Care programs for IBD increasingly emphasize mental health services despite a lack of robust trials to support these interventions, the investigators noted. Thus, their findings highlight “the need for researchers and clinicians to further develop and optimize the content and delivery of psychological programs for IBD patients.”

Tillotts Pharma and Boston Scientific provided partial funding, but had no other role in the study. The researchers reported having no relevant conflicts of interest.

SOURCE: Wynne B et al. Gastroenterology. 2018 Nov 16. doi: 10.1053/j.gastro.2018.11.030.

LA JOLLA, CALIF. – A retrospective study suggests patients with mycosis fungoides (MF) have an increased risk of developing hematologic and solid tumor malignancies.

Vidyard Video

Researchers found the risk of second malignancy was highest among MF patients aged 30 to 50 years and patients who had tumor stage or advanced stage MF.

The increased risk was present during the entire period after MF diagnosis, but it was greatest in the first 6 months after diagnosis and roughly a dozen years later.

Amrita Goyal, MD, of the University of Minnesota in Minneapolis, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.

The researchers first assessed the risk of second malignancy in 172 MF patients treated at UMN from 2005 to 2017, comparing this cohort to a control group of 172 patients with seborrheic dermatitis.

Second malignancies occurred in 24 MF patients and three controls, which was a significant difference (P = .0045). The most common second malignancies among the MF patients were melanoma (n = 4), prostate cancer (n = 3), and renal cell carcinoma (n = 3).

Further analyses revealed that MF patients were more likely to develop a second malignancy if they had tumor stage disease (P = .0024) or stage IIB or higher disease (P = .03).

To corroborate and expand upon these results, Dr. Goyal and her colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on patients diagnosed with MF from 2000 to 2014.

Among the 6,196 MF patients in this cohort, there were 514 second cancers.

“We found that MF patients were, overall, 10 times more likely to develop a second malignancy [compared with the general population],” Dr. Goyal said.

Specifically, the standardized incidence ratio was 10.15 for all malignancies, 7.33 for solid tumors, and 41.72 for hematologic malignancies.

Standardized incidence ratios for individual malignancies were:

• 69.8 for Hodgkin lymphoma.
• 46.5 for non-Hodgkin lymphoma.
• 8.6 for leukemia.
• 7.2 for melanoma.
• 6.2 for lung cancer.
• 7.9 for female breast cancer.
• 5.2 for colon cancer.
• 4.1 for prostate cancer.
• 3.9 for renal cell carcinoma.
• 3.8 for pancreatic cancer.
• 3.6 for bladder cancer.

“We found there is an increased risk [of second malignancy] during the first 6 months after diagnosis of MF, likely related to patients being in contact with the health care system more,” Dr. Goyal said. “Over time, patients have about a 7- to 10-fold increased risk over baseline, until they reach about 12 or 13 years after diagnosis, at which point, there is an increase in risk.”

The researchers found the greatest risk of second malignancy was among patients aged 30 to 50 years, although there was an increased risk for all age groups.

“The reason we think patients are experiencing an increased risk of cancers is we believe this may be due to immune suppression secondary to the mycosis fungoides, although further studies need to be performed to determine if that’s accurate,” Dr. Goyal said.

To that end, she and her colleagues are planning gene expression studies in patients from the UMN cohort. The researchers plan to examine genes involved in the pathogenesis of second malignancies and MF progression in tissue samples from 36 MF patients, 12 who developed second malignancies and 24 who did not.

The current research was funded by the American Society of Hematology. Dr. Goyal reported having no relevant financial disclosures. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – A retrospective study suggests patients with mycosis fungoides (MF) have an increased risk of developing hematologic and solid tumor malignancies.

Vidyard Video

Researchers found the risk of second malignancy was highest among MF patients aged 30 to 50 years and patients who had tumor stage or advanced stage MF.

The increased risk was present during the entire period after MF diagnosis, but it was greatest in the first 6 months after diagnosis and roughly a dozen years later.

Amrita Goyal, MD, of the University of Minnesota in Minneapolis, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.

The researchers first assessed the risk of second malignancy in 172 MF patients treated at UMN from 2005 to 2017, comparing this cohort to a control group of 172 patients with seborrheic dermatitis.

Second malignancies occurred in 24 MF patients and three controls, which was a significant difference (P = .0045). The most common second malignancies among the MF patients were melanoma (n = 4), prostate cancer (n = 3), and renal cell carcinoma (n = 3).

Further analyses revealed that MF patients were more likely to develop a second malignancy if they had tumor stage disease (P = .0024) or stage IIB or higher disease (P = .03).

To corroborate and expand upon these results, Dr. Goyal and her colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on patients diagnosed with MF from 2000 to 2014.

Among the 6,196 MF patients in this cohort, there were 514 second cancers.

“We found that MF patients were, overall, 10 times more likely to develop a second malignancy [compared with the general population],” Dr. Goyal said.

Specifically, the standardized incidence ratio was 10.15 for all malignancies, 7.33 for solid tumors, and 41.72 for hematologic malignancies.

Standardized incidence ratios for individual malignancies were:

• 69.8 for Hodgkin lymphoma.
• 46.5 for non-Hodgkin lymphoma.
• 8.6 for leukemia.
• 7.2 for melanoma.
• 6.2 for lung cancer.
• 7.9 for female breast cancer.
• 5.2 for colon cancer.
• 4.1 for prostate cancer.
• 3.9 for renal cell carcinoma.
• 3.8 for pancreatic cancer.
• 3.6 for bladder cancer.

“We found there is an increased risk [of second malignancy] during the first 6 months after diagnosis of MF, likely related to patients being in contact with the health care system more,” Dr. Goyal said. “Over time, patients have about a 7- to 10-fold increased risk over baseline, until they reach about 12 or 13 years after diagnosis, at which point, there is an increase in risk.”

The researchers found the greatest risk of second malignancy was among patients aged 30 to 50 years, although there was an increased risk for all age groups.

“The reason we think patients are experiencing an increased risk of cancers is we believe this may be due to immune suppression secondary to the mycosis fungoides, although further studies need to be performed to determine if that’s accurate,” Dr. Goyal said.

To that end, she and her colleagues are planning gene expression studies in patients from the UMN cohort. The researchers plan to examine genes involved in the pathogenesis of second malignancies and MF progression in tissue samples from 36 MF patients, 12 who developed second malignancies and 24 who did not.

The current research was funded by the American Society of Hematology. Dr. Goyal reported having no relevant financial disclosures. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – A retrospective study suggests patients with mycosis fungoides (MF) have an increased risk of developing hematologic and solid tumor malignancies.

Vidyard Video

Researchers found the risk of second malignancy was highest among MF patients aged 30 to 50 years and patients who had tumor stage or advanced stage MF.

The increased risk was present during the entire period after MF diagnosis, but it was greatest in the first 6 months after diagnosis and roughly a dozen years later.

Amrita Goyal, MD, of the University of Minnesota in Minneapolis, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.

The researchers first assessed the risk of second malignancy in 172 MF patients treated at UMN from 2005 to 2017, comparing this cohort to a control group of 172 patients with seborrheic dermatitis.

Second malignancies occurred in 24 MF patients and three controls, which was a significant difference (P = .0045). The most common second malignancies among the MF patients were melanoma (n = 4), prostate cancer (n = 3), and renal cell carcinoma (n = 3).

Further analyses revealed that MF patients were more likely to develop a second malignancy if they had tumor stage disease (P = .0024) or stage IIB or higher disease (P = .03).

To corroborate and expand upon these results, Dr. Goyal and her colleagues analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on patients diagnosed with MF from 2000 to 2014.

Among the 6,196 MF patients in this cohort, there were 514 second cancers.

“We found that MF patients were, overall, 10 times more likely to develop a second malignancy [compared with the general population],” Dr. Goyal said.

Specifically, the standardized incidence ratio was 10.15 for all malignancies, 7.33 for solid tumors, and 41.72 for hematologic malignancies.

Standardized incidence ratios for individual malignancies were:

• 69.8 for Hodgkin lymphoma.
• 46.5 for non-Hodgkin lymphoma.
• 8.6 for leukemia.
• 7.2 for melanoma.
• 6.2 for lung cancer.
• 7.9 for female breast cancer.
• 5.2 for colon cancer.
• 4.1 for prostate cancer.
• 3.9 for renal cell carcinoma.
• 3.8 for pancreatic cancer.
• 3.6 for bladder cancer.

“We found there is an increased risk [of second malignancy] during the first 6 months after diagnosis of MF, likely related to patients being in contact with the health care system more,” Dr. Goyal said. “Over time, patients have about a 7- to 10-fold increased risk over baseline, until they reach about 12 or 13 years after diagnosis, at which point, there is an increase in risk.”

The researchers found the greatest risk of second malignancy was among patients aged 30 to 50 years, although there was an increased risk for all age groups.

“The reason we think patients are experiencing an increased risk of cancers is we believe this may be due to immune suppression secondary to the mycosis fungoides, although further studies need to be performed to determine if that’s accurate,” Dr. Goyal said.

To that end, she and her colleagues are planning gene expression studies in patients from the UMN cohort. The researchers plan to examine genes involved in the pathogenesis of second malignancies and MF progression in tissue samples from 36 MF patients, 12 who developed second malignancies and 24 who did not.

The current research was funded by the American Society of Hematology. Dr. Goyal reported having no relevant financial disclosures. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – Phase 1 results suggest cobomarsen is well tolerated and can maintain or improve responses in patients with previously treated adult T-cell leukemia/lymphoma (ATLL).

Five of eight ATLL patients studied experienced disease stabilization or improvement while receiving cobomarsen (MRG-106), an inhibitor of microRNA-155.

There were no grade 3/4 adverse events (AEs) or serious AEs related to cobomarsen in these patients.

Francine Foss, MD, of Yale Cancer Center in New Haven, Conn., and her colleagues presented these results at the annual T-cell Lymphoma Forum.

In this ongoing trial (NCT02580552), researchers are evaluating cobomarsen in patients with B- and T-cell lymphomas, including mycosis fungoides and ATLL.

Results are available for eight patients with previously treated ATLL. These patients had received a median of 4 (range, 1-10) prior systemic therapies, and they had a median age of 51 years (range, 40-68).

The patients received three loading doses of cobomarsen during the first week of cycle 1, followed by weekly dosing. All patients have received cobomarsen as a 600 mg intravenous infusion. They can remain on cobomarsen until they progress, experience clinically significant side effects, cannot tolerate the drug, or the trial is terminated.

The researchers have measured efficacy at least monthly by monitoring tumor cell burden in the peripheral blood and lymph nodes, as well as evaluating changes in skin involvement.

Stabilization and response

“Initially, we saw some very good responses in patients who had escalating disease. In other words, their disease was progressing after conventional chemotherapy,” Dr. Foss said. “They went on this microRNA, [and] their disease stabilized and then regressed. We saw, subsequently, in another three or four patients, the same pattern of activity.”

In all, five patients achieved or maintained a response while on cobomarsen. All five were still receiving the drug at the data cutoff on Dec. 13, 2018.

Two of these patients had acute disease and were in partial response (PR) at baseline. These patients had received cobomarsen for 87 days and 401 days as of the data cutoff.

The other three patients still receiving cobomarsen at the cutoff had lymphomatous disease. At baseline, two of the patients were in PR and one had stable disease.

The two patients in PR at baseline had received cobomarsen for 80 days and 366 days at the data cutoff. The patient with stable disease had received the drug for 161 days.
 

Progression and withdrawal

There were three patients who withdrew from the study because of disease progression. Two of these patients were relapsing with significant skin involvement at baseline.

One of the patients discontinued cobomarsen after 23 days of treatment. The other patient received cobomarsen for 91 days and left the study, then re-enrolled and received cobomarsen for another 42 days before withdrawing from the study again.

The third patient had relapsed lymphomatous disease at baseline. This patient had a mixed response to cobomarsen, with some nodes decreasing in size and others increasing. She discontinued cobomarsen after 9 days.

“It’s still early on in our experience with ATLL, so we don’t really know yet who the patient is that’s going to respond – what are the clinical features that would predict response in these patients,” Dr. Foss said. “And we’re still really trying to understand how we give the drug to these patients, for how long, and whether or not we can change the dosing interval. But, nevertheless, we have some very interesting data.”
 

Safety

There were no dose-limiting toxicities, AE-related discontinuations, treatment-related grade 3/4 AEs, or new opportunistic infections observed.

“[I] have to say, in using this drug now for over a year in two of my patients – and that’s with weekly administration – we really haven’t seen anything as far as adverse events,” Dr. Foss said.

She noted that one patient has reported transient diarrhea after dosing.

Two serious AEs – febrile neutropenia and pyrexia – occurred in one patient, but neither of these events were considered related to cobomarsen. The AEs occurred after the patient had stopped cobomarsen, and both events resolved.

There were no on-treatment deaths. One patient (the one who received cobomarsen for 9 days) died from disease progression approximately 2 months after stopping cobomarsen and while on a different therapy.

Dr. Foss said, based on their results, she and her colleagues are hoping to accrue more ATLL patients in this trial.

The trial is sponsored by miRagen Therapeutics. Dr. Foss is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]

LA JOLLA, CALIF. – The spleen tyrosine kinase/Janus kinase inhibitor cerdulatinib has demonstrated activity against relapsed and refractory T-cell lymphomas.
 

Vidyard Video

In a phase 2 trial, cerdulatinib produced responses in 34% of patients with peripheral T-cell lymphoma (PTCL) and 26% of those with cutaneous T-cell lymphoma (CTCL).

The best responders were patients with angioimmunoblastic T-cell lymphoma, half of whom achieved a complete response (CR).

The most common grade 3 or higher adverse events (AEs) were amylase increase and lipase increase. However, these increases resolved with dose reduction or interruption, and there were no cases of clinical pancreatitis.

“The data is very encouraging,” said Tatyana Feldman, MD, of the John Theurer Cancer Center in Hackensack, N.J.

Dr. Feldman and her colleagues previously presented results from the phase 2 trial of cerdulatinib (NCT01994382) at the 2018 annual congress of the European Hematology Association.


Dr. Feldman and her colleagues presented data from expansion cohorts of the ongoing trial at the annual T-cell Lymphoma Forum. The cohorts included patients with PTCL or CTCL who had received at least one prior systemic therapy.

PTCL cohort

The 45 PTCL patients had a median age of 65 years (range, 21-84). They had received a median of 3 (range, 1-12) prior therapeutic regimens, 51% were refractory to their last therapy, and 27% had undergone stem cell transplant (SCT).

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 41 patients were evaluable for response.

The overall response rate was 34% (n = 14). Eleven patients had a CR, three had a partial response (PR), and nine had stable disease.

Responses according to subtype were as follows:

• 7 CRs and 1 PR in angioimmunoblastic T-cell lymphoma.
• 2 CRs in PTCL not otherwise specified.
• 1 CR in gamma-delta T-cell lymphoma.
• 1 PR in ALK-negative anaplastic large-cell lymphoma.
• 1 CR and 1 PR in adult T-cell leukemia/lymphoma.

Eight responders have remained on cerdulatinib for anywhere from 3 months to more than 12 months. Five patients have had a response lasting at least 6 months. One patient went on to SCT after achieving a CR.

The most common grade 3 or higher AEs observed in PTCL patients were amylase increase (n = 8), lipase increase (n = 6), pneumonia/lung infection (n = 5), neutropenia (n = 4), diarrhea (n = 4), febrile neutropenia (n = 4), abdominal pain (n = 4), sepsis/bacteremia (n = 3), anemia (n = 3), fatigue (n = 2), and pain (n = 1).

There were two grade 5 AEs – acute respiratory distress syndrome and pneumonia.
 

CTCL cohort

The 29 CTCL patients had a median age of 62 years (range, 24-79). They had received a median of 4 (range, 1-13) prior therapies, 55% were refractory to their last therapy, and 3% had undergone SCT.

The patients received cerdulatinib at 30 mg orally twice a day until progression or intolerance, and 27 were evaluable for response.

The overall response rate was 26% (n = 7). Two patients achieved a CR, five achieved a PR, and nine had stable disease. Responses occurred in mycosis fungoides and Sézary syndrome.

Eleven of 23 patients (48%) achieved at least a 50% reduction in skin lesions, and the researchers observed rapid improvements in pruritus.

“I saw patients who would take the first pill, and they would call me and say, ‘I no longer itch,’ ” Dr. Feldman said.

The most common grade 3 or higher AEs in CTCL patients were lipase increase (n = 11), amylase increase (n = 5), sepsis/bacteremia (n = 3), pain (n = 2), fatigue (n = 1), neutropenia (n = 1), and diarrhea (n = 1).

“It’s a very well-tolerated drug,” Dr. Feldman said, adding that there were “really no severe side effects which would prohibit the use of the drug.”

She noted that cerdulatinib’s “favorable” side effect profile might make it a promising candidate for use in combination regimens.

“I think it will be possible to combine it with other drugs in development in T-cell lymphoma. … immunological checkpoint inhibitors, epigenetic modulators such as HDAC [histone deacetylase] inhibitors, methylating agents, and PI3 kinase inhibitors,” Dr. Feldman said.

She reported having no disclosures relevant to this study. The trial is sponsored by Portola Pharmaceuticals.

The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.

[email protected]