Ruxolitinib cream ‘effective’ in reducing rashes, lesions caused by cutaneous GVHD
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Key takeaways:
- Topical ruxolitinib decreased rash size and severity in patients with cutaneous GVHD.
- Limited trial participation highlights the need for larger prospective study to confirm the study’s results.
Topical ruxolitinib cream significantly reduced skin manifestations caused by cutaneous graft-versus-host disease compared with vehicle cream, results from a randomized phase 2 study showed.
The findings, presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, revealed that topical ruxolitinib decreased the amount of affected body surface area (BSA) by nearly 30%, in addition to a 30% reduction in severity by 30%.
“Ruxolitinib cream was safe and effective compared to placebo in treating cutaneous graft-versus-host disease,” Alina Markova, MD, co-director of the adult and pediatric multidisciplinary graft-versus-host disease clinics at Memorial Sloan Kettering Cancer Center, said during her presentation.
Background and methodology
Ruxolitinib has already been approved as an oral treatment (Jakafi, Incyte) for acute GVHD and chronic GHVD, and as a topical therapy (Opzelura, Incyte) for eczema and vitiligo. Topical steroids have been the primary treatment for GVHD, but they produce “incomplete response” and toxicities that “may prompt systemic therapy,” Markova said.
Researchers conducted a prospective, double-blind trial to evaluate ruxolitinib 1.5% cream as a potential therapy.
Patients had to have an allogenic transplant, be at least 12 years old, have at least 2% BSA affected by cutaneous nonsclerotic and superficially sclerotic chronic GVHD, and be stable for at least 4 weeks if on systemic therapy to be eligible for the study.
All participants had half of their body treated with ruxolitinib and the other with vehicle cream. Researchers randomly assigned participants in a 1:1 ratio to determine which half of their bodies received treatment with ruxolitinib cream.
They chose to use vehicle cream over topical steroids as the alternative to ruxolitinib because efficacy data of steroids had not been established and most patients (88%) had already tried them, Markova said.
The trial cohort, enrolled between June 2019 and September 2022, consisted of 24 participants (54% women, 58.3% white), with a median age of 47.5 years (range, 18-78).
Most patients had an acute leukemia diagnosis (67%), classic chronic GVHD subtype (58%) and nonsclerotic cutaneous chronic GVHD (87%).
Efficacy at day 28 determined by BSA served as the study’s primary endpoint, and secondary endpoints included the Physician’s Global Assessment (PGA) of clinical condition, which allowed study investigators to evaluate improvement for each side of the body, and Composite Assessment of Index Lesion Disease Severity (CAILS), which evaluated erythema, scaling, pruritus and size.
Results
Ruxolitinib reduced affected BSA 57% by day 28 compared with 28% for the vehicle cream (P = .003). After the 4-week mark, participants received the option to use ruxolitinib as part of an open-label portion of the trial, and the vehicle-measured portion met the ruxolitinib treated area by day 56.
“Both had improved at that time, oftentimes to complete response,” Markova said.
She noted during a question-and-answer portion of her presentation that treatment did not affect participants with superficially sclerotic chronic GVHD as effectively as others.
“The ruxolitinib cream can help with some of the symptoms, the pruritus and sometimes the scaling, but oftentimes does not affect the course of the superficial sclerosis, so they typically require escalated systemic therapy for that,” she said in response to a question about treatment of deep sclerosis, where she detailed ruxolitnib had not delivered improvement in that group of patients off trial.
PGA determined ruxolitinib conferred a 62% improvement compared with 26% in the vehicle cream portion (P = .003) by day 28, and CAILS dropped 61% in the ruxolitinib portion compared to 31% in the vehicle side (P = .004).
Treatment-related adverse events occurred in 29% of patients, including a single grade 1 headache that possibly could have been attributed to the therapy, according to Markova. Unlikely reactions included one case of grade 5 CNS leukemia, which occurred “far off study,” Markova said. Researchers determined other adverse events to be unrelated to treatment.
“[Adverse events] were mild,” Markova concluded.
Follow-up questions
After Markova’s presentation, an attendee asked how much cream patients could use.
“Ruxolitinib cream is approved up to 20% body surface area, which, if you use that twice a day for multiple months over time, will equal about 1.3 mg of oral ruxolitinib absorption per day,” Markova said. “It’s not insignificant, but it’s obviously much lower than systemic dosing.”
Another wondered why the study had limited participation, which Markova attributed to the COVID-19 pandemic.
A larger prospective study should be conducted to continue and confirm the results of this study, she said.
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Markova A, et al. Abstract 1. Presented at: Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; Feb. 21-24, 2024; San Antonio.
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