Randomized phase 2 trial of topical ruxolitinib for chronic cutaneous graft-versus-host disease

A randomized phase 2 trial at Memorial Sloan Kettering Cancer Center (New York, NY) evaluated ruxolitinib 1.5% cream for epidermal or superficially sclerotic cutaneous chronic graft-versus-host disease (cGVHD). Patients aged 12 years or older with a history of allogeneic hematopoietic cell transplantation and cutaneous cGVHD involving at least 2% body surface area (BSA) were randomized to the body side receiving topical ruxolitinib twice daily for 28 days; placebo vehicle was applied to the contrateral lesional skin as control. The primary endpoint was the absolute day-28 between-side difference in affected lesional BSA; baseline between-side BSA differences were controlled for with adjusted mixed-effects regression. A total of 24 patients were randomized, with a median follow-up of 128 days (IQR 90-280). At day 28, 23 patients were evaluable (one patient did not start treatment). Mean affected lesional BSA changed from 14.3% (SD 7.9) at baseline to 6.2% (6.7) with ruxolitinib and from 14.5% (8.0) to 10.4% (9.1) with placebo vehicle ; after adjustment for baseline between-side affected BSA difference, the difference was -4.0 perentage points (95% CI -5.5 to -2.4; p<0.0010). Grade 3 or 4 treatment-emergent adverse events were CNS leukemia, sinusitis, and lung infection (one [4%] each); no treatment-related deaths occurred. The authors conclude that topical ruxolitinib showed significant clinical activity and a favorable harms profile in active cutaneous cGVHD. Ruxolitinib cream could represent a steroid-sparing, skin-directed alternative or second-line therapy.