Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

Those moles, skin tags, and liver spots should stay on your skin until you see a doctor, according to a new alert from the U.S. Food and Drug Administration. The alert warns against the use of over-the-counter products for removing moles, seborrheic keratoses (wart-like growths that are often brown), or skin tags, emphasizing that none are approved by the FDA for at-home use.

Dermatologists and the FDA say these products may lead to scarring and disfigurement.

Risks include “skin injuries, infection requiring antibiotics, scarring, and delayed skin cancer diagnosis and treatment,” according to the alert, which adds that the agency has received reports of people “who developed permanent skin injuries and infections after using products marketed as mole or skin tag removers. “

These products come in the form of gels, liquids, sticks, or ointments and commonly contain ingredients like salicylic acid, which are cytotoxic, or cell-killing. These chemicals are what make the products potentially dangerous, as each contains unregulated, and likely very high, amounts of these corrosive agents. Even products marketed as natural or organic have these same issues, said Adam Friedman, MD, professor and chief of dermatology at George Washington University, Washington, who notes that bloodroot is another ingredient found in these products.

Dr. Friedman explained that using these products without the supervision of a health care provider can create a chemical burn in the skin, leading to scarring. He’s treated patients for open wounds and infected ulcers caused by these products. “Over my career, I’ve seen many cases of patients coming in with self-inflicted harm due to using these quote, unquote, safe and natural products to remove benign, or even worse, potentially malignant neoplasms,” he told this news organization.

Another concern is that these spots on the skin are often the only sign of a serious issue – cancer. Early signs of melanoma, a type of skin cancer, include large, misshapen, or rapidly changing moles. Dr. Friedman said that if a patient uses one of these products on what is actually a cancerous mole, they will likely only remove the surface, and in turn, destroy the only sign of cancer – effectively killing the canary in the coal mine.

There’s a good chance that the root of the mole has been left intact under the skin surface, and as a result, the cancer has the potential to spread unnoticed. “If people aren’t going to a dermatologist to be properly diagnosed and properly managed, they’re going to cause more harm by thinking that they’ve taken care of a problem,” he said.

If you are concerned about any type of spot on your skin, a visit to the dermatologist will prove much simpler and safer for treating it than doing so at home. In the office, Dr. Friedman said, providers can use a range of highly studied techniques to remove skin lesions with minimal pain and scarring. From freezing, burning, snipping, or a quick moment under a scalpel, you’ll be healed in no time.

Anyone who has experienced an adverse event with one of these products and health care professionals should report cases to the FDA’s MedWatch Adverse Event Reporting Program.

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

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

For dermatologists and others treating patients with atopic dermatitis (AD), it is “an incredible time,” Lawrence F. Eichenfield, MD, said at MedscapeLive’s Women’s & Pediatric Dermatology Seminar.

More and more treatment options are available and even more are in the pipeline, said Dr. Eichenfield, professor of dermatology and pediatrics and vice chair of dermatology at the University of California, San Diego and Rady Children’s Hospital. As he put it: “We got pills, injections, things to smear on the skin.”

Those options are welcome and needed, as AD affects up to 20% of children and up to 10% of adults. The course is variable, as is severity, and quality of life is impacted.

Besides new treatment options, there is a new understanding about comorbidities, environmental effects, and triggers, Dr. Eichenfield said. Among the potential comorbidities health care providers should be aware of are allergies, such as food allergies; asthma; rhinitis; mental health issues (depression, anxiety, ADHD, learning disabilities, or in adults, substance abuse); bone health; skin infections; immune disorders such as alopecia areata or urticaria; and cardiovascular issues that could affect adults.

Environmental effects can play a role in aggravating AD, as providers learned after visits for AD increased after Northern California wildfires and also in other areas with high air pollution, Dr. Eichenfield said. “I actually discuss this with my families,” when making them aware of factors that may affect AD, he noted.

Dr. Eichenfield provided an overview of available treatment options, and what treatments may be coming next. Among the highlights:

Topical ruxolitinib: A JAK1,2 inhibitor in a cream formulation, it is now approved for patients with mild to moderate AD aged 12 years and older in the United States. Of the two strengths studied, the higher strength, 1.5%, was approved, Dr. Eichenfield said. How well did it work? In two phase 3 studies in patients aged 12 and older, of those on 1.5%, 53% were clear or almost clear at 8 weeks, versus 11% in the control group given the vehicle; 52% had at least a 4-point reduction in itch from baseline, versus 15.4% on vehicle. Quality of life improved in up to 73.2% of those given the medication versus 19.7% of those on the vehicle. There was a marked and quick improvement in itch, as early as 12 hours, and safety measures also look good, he said.

Topical tapinarof: Approved in May 2022, for adults with plaque psoriasis, phase 3 trials began in September, 2021, for adults and children with AD, according to the manufacturer. Activation of the aryl hydrocarbon receptor mediates its anti-inflammatory properties.

Topical roflumilast: A potent PDE-4 inhibitor, phase 3 AD studies are underway. It appears to be well tolerated, Dr. Eichenfield said.

Dupilumab: An IL-4/13 blocker, this biologic produced an itch reduction of 50% and EASI of 80%, improved quality of life, and reduced anxiety and depression. The drug “led the revolution in systemic therapy for atopic dermatitis,” he said. First approved for treating AD in patients aged 18 years and up in 2017, approval for patients 12 years and up followed in March 2019, then for age 6 years and up May 2020.

At the meeting on June 3, Dr. Eichenfield said that approval in children 5 years and under was imminent, and on June 7, the FDA approved dupilumab for use in children aged 6 months to 5 years. In a phase 3, 16-week trial, 28% of children treated with dupilumab added on to low-potency topical corticosteroids met the endpoint of clear or nearly clear skin, compared with 4% of those on the corticosteroids alone (P < .0001).

Tralokinumab: There is no approved indication yet for adolescents, but the injected biologic, an interleukin-13 antagonist, is approved for adults with moderate to severe AD who are not well-controlled with topicals, or who cannot use topicals.

Oral JAK inhibitors: These include abrocitinib and upadacitinib, both approved by the FDA in January 2022 for treating moderate to severe AD, and baricitinib (the latter not in the United States). “For AD, you probably won’t see it in the U.S.,” Dr. Eichenfield said, referring to baricitinib. However, it might get approved for alopecia areata, he noted.

Upadacitinib is approved for adolescents 12 and older with AD. Abrocitinib is approved for adults 18 and older with AD.

Regarding safety and tolerance concerns with oral JAK inhibitors, Dr. Eichenfield cites headache, acne, nausea, and upper respiratory tract infections as relatively common, while herpes zoster, venous thromboembolism, and lab anomalies (neutropenia, elevated CPK) are uncommon.

As the options for AD treatments increase, and expectations by families and clinicians change, Dr. Eichenfield said he often focuses on “bucket duty” – whether a specific patient should be in the topical bucket or the systemic one. It’s a decision that will continue to be crucial, he said.

When presented with treatment options, patients – and parents – often worry about side effects, said Vivian Shi, MD, associate professor of dermatology at the University of Arkansas Medical Center, Little Rock, who also spoke at the meeting. She gently tells them: “The worst side effect you can have is probably not treating the disease itself.”

Medscape Live and this news organization are owned by the same parent company. Dr. Eichenfield is a consultant or investigator for numerous companies that manufacture treatments for AD, but based his discussion on evidence-based recommendations and public presentations or publications.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

Deucravacitinib and orelabrutinib – two novel oral drugs under investigation for the treatment of systemic lupus erythematosus (SLE) – have performed well in early clinical trials reported as late-breaking abstracts at the annual European Congress of Rheumatology.

In the phase 2 PAISLEY study, up to 58% of patients treated with deucravacitinib versus 34% of placebo-treated patients met the primary study endpoint of an SLE Responder Index-4 (SRI-4) after 38 weeks of treatment. Deucravacitinib also “achieved or meaningfully improved” all of the secondary endpoints set out in the 363-patient trial and was reported to have a safety and tolerability profile that was generally similar to placebo.

“Deucravacitinib shows promise as a novel therapy for SLE and warrants further investigation in phase 3 trials,” said Eric F. Morand, MD, PhD, a clinical rheumatologist and head of the School of Clinical Sciences at Monash University in Melbourne.

In a separate, ongoing phase 1b/2a study designed to evaluate orelabrutinib as a potential treatment for SLE, no safety concerns were seen with the investigational drug, along with “trending efficacy,” that supports “further studies in larger and longer-term trials,” according to the study’s investigators.

“What sets these two new drugs apart from currently available targeted therapies are their mode of action,” said Md Yuzaiful Md Yusof, MBChB, PhD, who was not involved in either study.

“The results from the PAISLEY study are promising, and it’s good to see the patients recruited were of diverse ethnicity [50%–60% were White],” added Dr. Md Yusof, a senior research fellow within the Leeds (England) Institute of Rheumatic and Musculoskeletal Medicine and a consultant rheumatologist at Leeds Teaching Hospitals NHS Trust.

He noted that the placebo rate was also low: “This could be contributed to by keeping the background prednisolone dose low, which is often a challenge in designing SLE trials.”
 

Deucravacitinib – the distant cousin of the JAK family?

“Deucravacitinib is a compound you might not have heard of before,” Dr. Morand said.

“It’s an inhibitor of a kinase called TYK2, which, broadly speaking, is a member of JAK [Janus kinase] family,” he explained in an interview. TYK2 regulates signal transduction downstream of receptors for interleukin (IL)-23 and IL-12 pathways and the type I interferon family.

“It’s a very finite set of cytokine signals” that are being blocked with deucravacitinib, he said, adding that this means it’s more directly targeting SLE pathogenic mechanisms than perhaps other JAK inhibitor compounds.

“It also means that it shouldn’t have some of the downsides of the other JAK inhibitors,” Dr. Morand said, “such as hematopoietic side effects, including cytopenias.”
 

The phase 2 PAISLEY study

This study involved 363 patients with moderate to severe, active SLE were recruited and randomized to receive placebo (n = 90) or one of three doses of deucravacitinib: 3 mg twice daily (n = 91), 6 mg twice daily (n = 93), or 12 mg once daily (n = 89). Most patients were also taking multiple background therapies, but this was similar across the four treatment arms.

The SRI-4 primary endpoint after 38 weeks of treatment was met by 34.4% of patients who received placebo, but 58.2% of those treated with deucravacitinib 3 mg twice daily (P = .0006 versus placebo), 49.5% (P = .021) of those treated with 6 mg twice daily, and 44.9% (P = .078) treated with 12 mg once daily.

“All secondary outcome measures were achieved or meaningfully improved at week 48, including SRI-4, BICLA [British Isles Lupus Assessment Group-based Composite Lupus Assessment], low-level disease activity state [LLDAS], reduction in skin disease and reduction in arthritis,” Dr. Morand said.

In addition, early biomarker results showed reductions in double-stranded DNA titers and increases in serum C4 complement with deucravacitinib across the duration of the study.

In discussion, Dr. Morand was asked about the seemingly negative or inverse dose response seen in the trial, with the best results seen with the 3-mg twice daily dose, then lower effects seen with two higher doses.

“Our analysis is that it’s not an inverse dose response, but rather a flat dose response above the 3-mg [twice daily] dose,” he said, noting that there was a higher dropout rate because of adverse effects in the 12-mg once daily group and those participants were recorded as nonresponders.

“We think what we’ve seen here is that 3 mg twice daily is a sufficient dose and there was no additional therapeutic gain above that.”

Rates of adverse events (AEs), serious AEs, and AEs of interest were overall fairly similar between deucravacitinib and placebo groups. The most common side effects seen with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. Skin reactions, such as acne, rash, and pruritis, among others, were more common in deucravacitinib- than in placebo-treated patients.

Importantly, Dr. Morand noted that there were no major cardiac events or thrombotic events and no deaths seen in the study. There was no signal for an increase in serious or opportunistic infections, including herpes zoster. There was no effect on common laboratory parameters.

“These are very encouraging results for patients with SLE,” Albert Roy, executive director of Lupus Therapeutics, said in a press release issued by the Lupus Research Alliance.

“We are honored to have played a role in this exciting work by helping to conduct this clinical trial through our Lupus Clinical Investigators Network of renowned North American academic centers.”

In an interview, he added: “We’re cautiously optimistic. Hopefully, if it continues to progress through phase 3, it’ll be the first oral agent that would be approved for lupus, notwithstanding prednisone and Plaquenil [hydroxychloroquine], back in the 50s.”

Orelabrutinib phase 2 study in SLE

Another approach to oral route of administration under investigation in SLE is the use of orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) that was approved in China in December 2020 for the treatment of certain lymphomas and leukemias.

The rationale for testing it in SLE comes from two preclinical studies that had suggested a possible benefit in reducing disease activity, explained Zhanguo Li, MD, PhD, professor at Peking University People’s Hospital in Beijing. He presented the results of an ongoing randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study comparing three different doses of orelabrutinib (50, 80, and 100 mg, once daily) to placebo.

As in the deucravacitinib trial, the SRI-4 was used to assess the potential efficacy of orelabrutinib, although in a much smaller patient population (n = 92) and at a shorter time point (12 weeks). Results showed an 11%-20% difference between the percentage of patients who met SRI-4 response criteria with orelabrutinib and those on placebo, at a respective 46.5%, 53.3%, 56.3% and 35.7%.

SLE Disease Activity Index (SLEDAI) scores showed a similar benefit of orelabrutinib over placebo, with 54%-63% and 30% of patients, respectively, achieving a score of 8 or more.

Adverse event rates were similar to those of placebo with most events being of mild or moderate nature. Three patients treated with orelabrutinib experienced serious adverse events, of which one was grade 3, but there were no reported deaths.

Pharmacokinetic and pharmacodynamic data showed a dose effect, and nearly complete occupancy of BTK was achieved at all dose levels for 24 hours, consistent with once-daily dosing.

“BTK plays an important role in B-cell regulation, thus B-cell and myeloid-cell blockade through BTK inhibition is an interesting potential new target for SLE,” Dr. Md Yusof said.

“Data from this early dose-ranging trial is encouraging. No major safety signal apart from mild reduction in lymphocyte and white cell counts,” he added.

“There are still plenty of challenges ahead for this drug’s development, particularly as none of the BTK inhibitors have yet to succeed in phase 3 trials in rheumatic and musculoskeletal diseases,” Dr. Md Yusof said.

Early days for both agents

While both seem currently promising, it’s very early days for deucravacitinib and orelabrutinib as possible new agents for SLE.

Aside from SLE, deucravacitinib is being tested across multiple immune-mediated diseases. This includes psoriasis, where two phase 3 trials – POETYK PSO-1 and POETYK PSO-2 – have already been completed, and psoriatic arthritis, where a phase 2 trial has been reported; all with positive results.

Phase 3 testing of deucravacitinib will go ahead and recruitment may start toward the end of this year, but it’ll take years to complete the studies, Dr. Morand said. Even if the trials prove positive, neither agent is going to be available for clinical use for several years.

A case in point is anifrolumab (Saphnelo), which Dr. Morand was involved in assessing. Despite gaining approval in the United States and across much of the world, the drug still going through reimbursement processes.

“The trial data, and lots of post hoc analysis, show clearly that it’s a major step forward in treating lupus,” he said in an interview, but “access is limited in most places, so hands-on experience with that new treatment is still limited for most clinicians.”

As for all the other new targeted approaches under investigation, “although there’s a lot of trial activity, there’s still a couple of years away before any of the current trials deliver new treatment. That’s if they provide positive findings. Indeed, there have been numerous agents that have shown promise at phase 2 but then fall at the final phase 3 hurdle, including baricitinib, which Dr. Morand reported on in a separate poster presentation.

Phase 3 data proved disappointing: “Results are not sufficiently positive for that to go forward,” he said, adding that “transitioning from a successful phase 2 to a successful phase 3 is challenging, and many products have failed.”

Dr. Morand added: “It’s a very exciting time to be in lupus research, and there’s a lot of optimism about the future. But when I go back to my clinic tomorrow, I treat my patients exactly the same as I did last week and last year.”

It’s yet to be seen if deucravacitinib will fulfill its early promise, but it’s off to an impressive start. A positive for patients is that it’s an oral drug, with the potential to improve access to treatment across the world where getting infusions may be an issue.

“These are some of the most exciting data that I’ve seen at the phase 2 level in terms of effect size across all the readouts that are used,” Dr. Morand said. “There’s no guesswork here; it worked across all the measures. That’s very reassuring.”

The PAISLEY study was sponsored by Bristol-Myers Squibb. Dr. Morand has acted as a consultant to the company and received research support for the conduct of the trial. He disclosed acting as a consultant or receiving research funding from AbbVie, Amgen, AstraZeneca, Biogen, Eli Lilly, EMD Serono, Janssen, Genentech, Servier, Novartis, and UCB. Mr. Roy is the executive director of Lupus Therapeutics, which manages the Lupus Clinical Investigators Network based in North America. Lupus Therapeutics is the clinical trials arm of the Lupus Research Alliance, a nongovernmental, nonprofit funder of lupus research worldwide. The orelabrutinib study was sponsored by InnoCare Pharma. Dr. Li is the principal investigator for the trial but had no conflicts of interest to declare. Dr. Md Yusof disclosed receiving consultancy fees from Aurinia Pharmaceuticals.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

NEW ORLEANS – In an unexpected finding, researchers discovered that Asian American adolescents had the highest rate of suicidal ideation, per a 2019 national survey of high-school students. According to a weighted analysis, 24% of Asian Americans reported thinking about or planning suicide vs. 22% of Whites and Blacks and 20% of Hispanics (P < .01).

“We were shocked,” said study lead author Esha Hansoti, MD, who conducted the research at UT Southwestern Medical Center, Dallas, and is now a psychiatry resident at Zucker Hillside Hospital Northwell/Hofstra in Glen Oaks, NY. The findings were released at the annual meeting of the American Psychiatric Association.

Dr. Hansoti and colleagues launched the analysis in light of sparse research into Asian American mental health, she said. Even within this population, she said, mental illness “tends to be overlooked” and discussion of the topic may be considered taboo.

For the new study, researchers analyzed the 2019 Youth Risk Behavior Survey, conducted biennially by the Centers for Disease Control and Prevention, which had more than 13,000 participants in grades 9-12.

A weighted bivariate analysis of 618 Asian American adolescents – adjusted for age, sex, and depressive symptoms – found no statistically significant impact on suicidal ideation by gender, age, substance use, sexual/physical dating violence, or fluency in English.

However, several groups had a statistically significant higher risk, including victims of forced sexual intercourse and those who were threatened or bullied at school.

Those who didn’t get mostly A grades were also at high risk: Adolescents with mostly Ds and Fs were more likely to have acknowledged suicidal ideation than those with mostly As (adjusted odds ratio [AOR] = 3.2).

Gays and lesbians (AOR = 7.9 vs. heterosexuals), and bisexuals (AOR = 5.2 vs. heterosexuals) also showed sharply higher rates of suicidal ideation.

It’s not clear why Asian American adolescents may be at higher risk of suicidal ideation. The survey was completed prior to the COVID-19 pandemic, which spawned bigotry against people of Asian descent and an ongoing outbreak of high-profile violence against Asian Americans across the country.

Dr. Hansoti noted that Asian Americans face the pressures to live up to the standards of being a “model minority.” In addition, “very few Asian American adolescents are taken to a therapist, and few mental health providers are Asian Americans.”

She urged fellow psychiatrists “to remember that our perceptions of Asian Americans might hinder some of the diagnoses we could be making. Be thoughtful about how their ethnicity and race affects their presentation and their own perception of their illness.”

She added that Asian Americans may experience mental illness and anxiety “more somatically and physically than emotionally.”

In an interview, Anne Saw, PhD, associate professor of clinical-community psychology at DePaul University, Chicago, said the findings are “helpful for corroborating other studies identifying risk factors of suicidal ideation among Asian American adolescents. Since this research utilizes the Youth Risk Behavior Survey, these findings can be compared with risk factors of suicidal ideation among adolescents from other racial/ethnic backgrounds to pinpoint general as well as specific risk factors, thus informing how we can tailor interventions for specific groups.”

According to Dr. Saw, while it’s clear that suicide is a leading cause of death among Asian American adolescents, it’s still unknown which specific subgroups other than girls and LGBTIA+ individuals are especially vulnerable and which culturally tailored interventions are most effective for decreasing suicide risk.

“Psychiatrists should understand that risk and protective factors for suicidal behavior in Asian American adolescents are multifaceted and require careful attention and intervention across different environments,” she said.

No funding and no disclosures were reported.

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

Following tumor removal in patients with recurrent glioblastoma, an absorbable collagen tile can deliver a controlled and therapeutic dose of radiation that targets remaining tumor cells and spares healthy tissue, new research suggests.

The results showed inserting a collagen matrix containing radioactive seeds into the brain postsurgery did not impede wound healing. It also showed a favorable safety profile, researchers note.

Benefits for patients undergoing this GammaTile (GT) intervention include not having to wait weeks to receive radiation treatment, which in turn improves their quality of life, said study investigator Clark C. Chen, MD, PhD, chair, department of neurosurgery, University of Minnesota Medical School, Minneapolis.

“These initial results are highly promising and offer hope for patients afflicted with an otherwise devastating disease,” Dr. Chen said in an interview.

If replicated in larger trials, GT therapy “could define a new standard of care, and there would really be no reason why patients shouldn’t get this therapy,” he added.

This is the first clinical series describing GT use since its approval by the U.S. Food and Drug Administration (FDA) for recurrent brain cancer.

The findings were presented at the annual meeting of the American Association of Neurological Surgeons (AANS) and were published recently in Neuro-Oncology Advances.

Radioactive seeds

GT therapy is a version of brachytherapy where radioactive sources are placed adjacent to cancerous tissue. It consists of radioactive seeds embedded with a collagen tile.

The neurosurgeon inserts these “tiles” immediately after tumor removal to cover the entire resection cavity, Dr. Chen said. The tiles maintain the cavity architecture to prevent radiation “hot spots” associated with cavity collapse.

Dr. Chen noted the therapy is “short range,” with most of the radiation delivered within 8 millimeters of the radioactive seeds.

The radiation lasts for about a month and the collagen tiles are eventually absorbed within the body. “You put in the tiles and you don’t need to do anything more,” Dr. Chen said.

GT has a number of advantages. Unlike with traditional brachytherapy, the collagen tile provides a buffer around the radiation sources, allowing delivery of the optimal radiation dose while preserving healthy tissue.

It also avoids the up-to-6-weeks patients have to wait postsurgery to get external beam radiation therapy. “If you start radiation too early, it actually compromises wound healing, and in the meantime the tumor is growing,” said Dr. Chen.

“I have several patients where I removed a large tumor and within that 6-week period, the tumor came back entirely,” he added.

With the gamma-tile, however, radiation from the seeds kills the tumor while the body heals.

Safety profile

The study included 22 patients (mean age, 57.7 years; 15 men, 7 women) with wild-type isocitrate dehydrogenase glioblastoma. They were all having surgery for recurrent tumors.

“One of the most challenging aspects of glioblastomas is that not only do the tumors come back, they come back immediately adjacent to where you have done the surgery, and for many patients this is demoralizing,” Dr. Chen said.

Six participants had 0 ⁶ -Methylguanine-DNA methyltranferase (MGMT) methylated glioblastoma, while the others had unmethylated MGMT.

The mean follow-up from initial diagnosis was 733 days (2 years).

Results showed one patient had to be readmitted to the hospital for hydrocephalus, but there were no re-admissions within 30 days attributable to GT.

Despite participants having undergone a second and third resection through the same surgical incision, there were no wound infections. “One of the concerns of giving radiation right after surgery is it can compromise wound healing, and this is why you wait 6 weeks,” Dr. Chen noted.

He stressed that no patient in the study suffered from adverse radiation effects that required medical or surgical intervention.

As the radiation is so short-range, hair loss and skin irritation are not side effects of GT, he added.

“The radiation is inside the brain and highly targeted, so it doesn’t hit hair follicles,” said Dr. Chen. “As best as I can observe in these patients, I did not see toxicity associated with radiation.”

One and done

Among the 22 participants, 18 had neurologic symptoms at baseline. There were no new neurologic deficits that developed after GT placement.

In addition, GT therapy improved “local control” — preventing the tumor from growing back at the site of the surgery. The local control was 86% at 6 months and 81% at 12 months.

The median progression-free survival was about 8 months. The median overall survival was 20 months (about 600 days) for the unmethylated MGMT group and 37.4 months (about 1120 days) for the methylated group.

Outcomes compared favorably to an independent glioblastoma cohort of similar patients who did not receive GT treatment during the study period, Dr. Chen noted.

“This therapy can potentially redefine how we treat glioblastoma patients whose cancer came back,” he said.

A study limitation was that it did not include quality-of-life data, which makes it challenging to assess the therapy’s overall impact, Dr. Chen said. However, he added that from his experience, patients very much appreciate not having to repeatedly take time off work for clinic or hospital visits to receive radiation treatments.

“One of the beauties of this therapy is it’s a one-and-done deal,” he said.

Interesting, timely

Commenting for this news organization, William T. Curry Jr, MD, co-director at MassGeneral Neuroscience and director of neurosurgical oncology at Mass General Cancer Center, Boston, called the study “interesting and timely.”

These new data “underscore that GT is safe in patients that have undergone gross total resection of recurrent glioblastoma and that rates of progression free survival may exceed those treated with resection alone,” said Dr. Curry, who was not involved with the research.

“Surgeons are excited about anything that has the potential to improve outcomes for patients with this very challenging disease, and it is wonderful to be able to offer hope and survival tools to patients,” he added.

However, Dr. Curry noted there are challenges and potential biases when studying survival in cancer patients without conducting a randomization process. The investigators “admit to methodological flaws inherent in the single-arm design in a patient population with recurrent glioblastoma not treated uniformly,” he said.

In addition, he noted overall survival may not have been related to the GT intervention. “Multicenter randomization is probably required to get to the bottom of the survival advantage in different subsets of glioblastoma patients,” Dr. Curry said.

Further research is needed to confirm the efficacy, appropriate indications, and timing of the intervention, but “I would support a randomized multicenter study in patients undergoing near gross total resection of recurrent glioblastoma,” he concluded.

The study received no outside funding. Dr. Chen and Dr. Curry have disclosed no relevant financial relationships.

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

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

The American Society for Radiation Oncology (ASTRO) has issued new guidance on the use of radiation therapy for the treatment of brain metastases, an update on its 2012 document.  

“In the decade since the previous ASTRO brain metastases guideline, there has been a tremendous evolution in the way we manage patients’ disease,” said Paul D. Brown, MD, chair of the guideline task force and a professor of radiation oncology at the Mayo Clinic in Rochester, Minn.  

“The development of stereotactic radiosurgery (SRS) has allowed treatment of limited brain metastases alone, often in a single fraction, while largely sparing the surrounding brain,” he elaborated in a statement. Also, novel techniques such as hippocampal avoidance with whole-brain radiation can greatly improve quality of life, he added.

The guideline was published May 6 in Practical Radiation Oncology.

“With the emergence of novel radiotherapy techniques and technologies, brain-penetrating drug therapies and neurosurgical interventions, modern management of brain metastases has become increasingly personalized, complex and multidisciplinary,” Vinai Gondi, MD, vice chair of the guideline task force and director of research and education at the Northwestern Medicine Cancer Center and Proton Center in Chicago, said in a statement.

“We developed this guideline to help inform and guide clinicians in patient-centered, multidisciplinary care for their patients with brain metastases,” he added.

Key recommendations

Overall, the recommendations address a wide range of topics related to radiation therapy in patients with cancer that has spread to the brain,  including delivery techniques for radiation therapy to manage both unresected and resected brain metastases. The guideline also includes treatment algorithms for limited brain metastases and extensive brain metastases.

Key recommendations are as follows:

For patients with intact/unresected brain metastases:

• SRS is recommended for patients with 1-4 brain metastases and reasonable performance status (ECOG performance status 0-2); SRS is conditionally recommended for those with 5-10 brain metastases and reasonable performance status; for patients with tumors exerting mass effect and/or larger size, multidisciplinary discussion with neurosurgery to consider surgical resection is suggested.
• Upfront local therapy (radiation and/or surgery) is strongly recommended for patients with symptomatic brain metastases. 
• For patients with asymptomatic brain metastases who are eligible for central nervous system-directed systemic therapy, multidisciplinary and patient-centered decision-making to determine whether local therapy may be safely deferred is conditionally recommended.
• Whole brain radiation therapy (WBRT) is recommended as a primary treatment for patients with favorable prognosis who have brain metastases that are ineligible for surgery and/or SRS. Hippocampal avoidance (HA) is recommended when appropriate to preserve memory function, as is the addition of memantine to delay neurocognitive decline. Adjuvant WBRT added to SRS routinely is not recommended.
• Supportive care only, without WBRT, should be considered for patients with poor prognosis and brain metastases. Reasonable options for this population include palliative care or hospice, or short-course WBRT for symptomatic brain metastases
• Recommendations also include guidance for SRS and WBRT dosing as well as the use of single-fraction vs hypofractionated SRS. Although SRS use is driven by the number of brain metastases, it is critical that other important factors (eg, total tumor volume and location, patient age, and extracranial disease status) should be taken into consideration during patient-centered decision-making by the multidisciplinary team.

For patients with resected brain metastases:

• Radiation therapy is recommended for all patients after resection in order to improve intracranial control.
• For patients with limited brain metastases after resection, postoperative SRS is recommended over WBRT to preserve the patient’s neurocognitive function and quality of life.
• As a potential alternative to SRS postresection, SRS prior to brain metastasis resection is conditionally recommended.

Updating the guidelines

ASTRO emphasizes that the scope of this paper is limited to the radiotherapeutic management of intact and resected brain metastases resulting from nonhematologic solid tumors. It provides guidance on the reasonable use of modern radiation therapy strategies, including single-fraction and fractionated (ie, hypofractionated SRS) SRS and HA-WBRT, and also discusses clinical considerations in selecting the optimal radiation therapy strategy or in deferring it in favor of best supportive care or close neuro-oncologic surveillance.

The authors note, however, that beyond the scope of this guideline, there are many other important questions that may be the subject of other guidance, such as the appropriate role for CNS-active systemic therapies and/or surgical intervention.

A version of this article was first published on Medscape.com.

Lisocabtagene maraleucel, a novel chimeric antigen receptor (CAR) T-cell product, evoked a clinical response in patients with relapsed or refractory large B-cell lymphoma in a pilot study presented at the annual meeting of the American Society of Clinical Oncology.

Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.

Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.

In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.

For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.

The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.

“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.

The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.

Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.

“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.

The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.

Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.

The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
 

Addressing an ongoing unmet need

In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”

Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.

“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.

CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”

However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”

An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
 

Liso-cel may fill treatment gap as second-line therapy

The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.

“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.

“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.

“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.

Dr. Till had no relevant financial conflicts to disclose.

The study was funded by Bristol Myers Squibb.

Lisocabtagene maraleucel, a novel chimeric antigen receptor (CAR) T-cell product, evoked a clinical response in patients with relapsed or refractory large B-cell lymphoma in a pilot study presented at the annual meeting of the American Society of Clinical Oncology.

Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.

Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.

In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.

For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.

The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.

“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.

The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.

Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.

“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.

The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.

Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.

The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
 

Addressing an ongoing unmet need

In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”

Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.

“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.

CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”

However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”

An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
 

Liso-cel may fill treatment gap as second-line therapy

The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.

“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.

“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.

“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.

Dr. Till had no relevant financial conflicts to disclose.

The study was funded by Bristol Myers Squibb.

Lisocabtagene maraleucel, a novel chimeric antigen receptor (CAR) T-cell product, evoked a clinical response in patients with relapsed or refractory large B-cell lymphoma in a pilot study presented at the annual meeting of the American Society of Clinical Oncology.

Not all patients with relapsed or refractory large B cell lymphoma (r/r LBCL) are candidates for high-dose chemotherapy or hematopoietic stem cell transplantation (HSCT), and options for second-line therapies for this population are limited, said Dr. Alison Sehgal of the University of Pittsburgh Medical Center in her presentation of the findings.

Lisocabtagene maraleucel (liso-cel) is a CD19-directed CAR T-cell product. In a previous phase 3 randomized trial (the TRANSFORM study), lisocabtagene showed superiority over salvage chemotherapy for LBCL patients who were fit candidates for stem cell transplant, but its use in older, frail patients who are not transplant candidates remains uncertain, wrote Dr. Sehgal and colleagues in their poster at the meeting.

In the study, the researchers identified 74 patients with r/r LBCL. Of these, 61 were treated with liso-cel. The patients ranged in age from 53 to 84 years, with a median age of 74 years, 61% were male, and 89% were white. Approximately half were refractory and half were relapsed.

For the therapy, patients underwent lymphodepletion with cyclophosphamide and fludarabine, followed 2-7 days later by an infusion of liso-cel at a target dose of 100 x 106 CAR+ T cells; all patients had at least 6 months of follow-up from their first response.

The primary endpoint of overall response rate occurred in 80% of the patients, and clinically meaningful complete response occurred in 54% over a median follow-up of 12.3 months.

“Clinically meaningful CRs were observed across all subgroups,” Dr. Sehgal said in her presentation.

The response lasted a median of 21.7 months, and the median follow-up for duration of response was 15.5 months. The median overall survival was not reached, but the median progression-free survival was 9.0 months, with a median follow-up period of 13.0 months.

Responses occurred across all prespecified subgroups, with no significant differences in either safety or efficacy based on hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores.

“Despite the advanced age and comorbidities of the population, the safety profile was consistent with previous reports,” and no new or increased safety signals appeared, Dr. Sehgal said.

The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Cytokine-release syndrome (CRS) occurred in 23 patients (38%); of these, 1 patient was grade 3 and none were grades 4 or 5.

Approximately one-third of the patients (31%) experienced neurological events during the study; three cases were grade 3, none were grades 4 or 5. Patients with CRS or NE were treated with tocilizumab (10%), corticosteroids (3%), or both (20%). Treatment-emergent adverse events of grade 3 or higher occurred in 79% of patients overall, including grade 5 events in two patients because of COVID-19.

The study findings were limited by the small sample size and lack of controls. However, the results support the potential use of liso-cel as a second-line therapy for r/r LBCL patients who are not candidates for HSCT, Dr. Sehgal concluded.
 

Addressing an ongoing unmet need

In an interview, study coauthor Dr. Leo I. Gordon of Northwestern University, Chicago, observed, “Patients with relapsed or refractory large B-cell lymphoma who are not considered candidates for stem cell transplant following first-line treatment, based on age, comorbidities, health status, or other prognostic factors, have more difficult-to-treat disease, poor prognosis, and more limited treatment options.”

Dr. Gordon noted that the PILOT study is the only trial to evaluate a CAR T-cell therapy as a second-line treatment for r/r LBCL patients who are not considered candidates for stem cell transplant.

“Data from the primary analysis of the PILOT study further demonstrate the potential value of using CAR T-cell therapies earlier in the treatment paradigm for relapsed or refractory LBCL to help improve clinical outcomes and address ongoing unmet need,” he said.

CAR T-cell therapies have shown benefits in later lines for r/r LBCL and as a second-line treatment for r/r LBCL patients who are deemed candidates for stem cell transplant, “so we were encouraged and not surprised by these data.”

However, Dr. Gordon noted, “There may be some patients with similar presentations that might have a transplant, so one limitation of the trial is how one defines patients where transplant is the intended therapy, and that assessment varies among institutions and clinicians.”

An application for liso-cel as a treatment for patients with r/r LBCL who have failed front-line therapy is currently under Priority Review with the FDA, with a Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022, he added.
 

Liso-cel may fill treatment gap as second-line therapy

The current study is important because “the long-term outcomes of patients with relapsed or refractory large B-cell lymphoma who are not candidates for stem cell transplantation is very poor,” said Dr. Brian Till of Fred Hutchinson Cancer Research Center, Seattle, in an interview.

“CAR T therapy leads to about a 40% cure rate, but is currently only available in this population after the failure of second-line therapy,” said Dr. Till, who was not involved in the study.

“Given that liso-cel was shown to improve outcomes in the second-line setting among transplant candidates, it is logical to consider it as second-line therapy in nontransplant candidates as well, who are otherwise fit enough to receive CAR T therapy,” Dr. Till explained.

“This study showed a rate of long-term progression-free survival similar to what has been observed in the third-line setting and was reasonably well tolerated in these older patients,” said Dr. Till. The results suggest “that second-line liso-cel may be an attractive treatment strategy for patients who are not candidates for stem cell transplantation due to advanced age or comorbidities,” he noted.

Dr. Till had no relevant financial conflicts to disclose.

The study was funded by Bristol Myers Squibb.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.

Emergency contraception is more likely to fail in women with obesity, but simply doubling the dose of levonorgestrel (LNG)-based contraception does not appear to be effective according to the results of a randomized, controlled trial.

Alison B. Edelman, MD, MPH, of the department of obstetrics & gynecology at Oregon Health & Science University, Portland, led the study published online in Obstetrics & Gynecology.

The researchers included healthy women ages 18-35 with regular menstrual cycles, body mass index (BMI) higher than 30 kg/m², and weight at least 176 pounds in a randomized study.

After confirming ovulation, researchers monitored participants with transvaginal ultrasonography and blood sampling for progesterone, luteinizing hormone, and estradiol every other day until a dominant follicle 15 mm or greater was seen.

At that point the women received either LNG 1.5 mg or 3 mg and returned for daily monitoring up to 7 days.

Emergency contraception with LNG works by preventing the luteinizing hormone surge, blocking follicle rupture. The researchers had hypothesized that women with obesity might not be getting enough LNG to block the surge after oral dosing.

Previous trials had shown women with obesity had a fourfold higher risk of pregnancy, compared with women with normal BMI taking emergency contraception.

The primary outcome in this trial was whether women had follicle rupture 5 days after dosing.

The authors wrote: “The study had 80% power to detect a 30% difference in the proportion of cycles with at least a 5-day delay in follicle rupture (50% decrease).”

A total of 70 women completed study procedures. The two groups (35 women in each) had similar demographics (mean age, 28 years; BMI, 38).

No differences found between groups

“We found no difference between groups in the proportion of participants without follicle rupture,” the researchers wrote.

More than 5 days after dosing, 51.4% in the lower-dose group did not experience follicle rupture. In the double-dose group 68.6% did not experience rupture but the difference was not significant (P = .14).

Among participants with follicle rupture before 5 days, the time to rupture – the secondary endpoint – also did not differ between groups.

The researchers concluded that more research on the failures of hormonal emergency contraception in women with obesity is needed.

Eve Espey, MD, MPH, distinguished professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, said in an interview that the study was well designed and the results “form a strong basis for clinical recommendations.”

“Providers should not recommend a higher dose of LNG emergency contraception for patients who are overweight or obese, but rather should counsel patients on the superior effectiveness of ulipristal acetate for those seeking oral emergency contraception as well as the longer time period after unprotected sex – 5 days – that ulipristal maintains its effectiveness.”

“Providers should also counsel patients on the most effective emergency contraception methods, the copper or LNG intrauterine device,” she said.

She said the unique study design of a pharmacodynamic randomized controlled trial adds weight to the findings.

She and the authors noted a limitation is the use of a surrogate outcome, ovulation delay, for ethical and feasibility reasons, instead of the outcome of interest, pregnancy.

The trial was conducted at Oregon Health & Science University and Eastern Virginia Medical School, Norfolk, from June 2017 to February 2021.

Study enrollees were compensated for their time. They were required not to be at risk for pregnancy (abstinent or using a nonhormonal method of contraception).

Dr. Edelman reported receiving honoraria and travel reimbursement from the American College of Obstetricians and Gynecologists, the World Health Organization, and Gynuity for committee activities and honoraria for peer review from the Karolinska Institute. She receives royalties from UpToDate. Several coauthors have received payments for consulting from multiple pharmaceutical companies. These companies and organizations may have a commercial or financial interest in the results of this research and technology. Another was involved in this study as a private consultant and is employed by Gilead Sciences, which was not involved in this research.