Ruxolitinib 1.5% cream (Opzelura) reduced affected lesional body surface area (BSA) more than placebo vehicle at day 28 in patients with epidermal or superficially sclerotic cutaneous chronic graft-vs-host disease (cGVHD), according to findings from a single-center, randomized, double-blind, intra-patient–controlled phase 2 trial (NCT03954236) published in The Lancet Haematology.1
Findings also showed that the topical JAK1/2 inhibitor also improved clinician-assessed global and lesion-severity scores, with no treatment-related deaths and no treatment interruptions or dose modifications due to toxicity.
Among evaluable patients at day 28 (n = 23), each of whom had one body side treated with ruxolitinib and the contralateral side treated with placebo vehicle (ruxolitinib side, n = 23; vehicle side, n = 23), mean affected lesional BSA decreased from 14.3% (standard deviation [SD], 7.9) at baseline to 6.2% (SD, 6.7) on the ruxolitinib-treated side vs from 14.5% (SD, 8.0) to 10.4% (SD, 9.1) on the vehicle-treated side (difference, –4.2%; 95% CI, –6.8% to –1.5%; P = .0030). These changes corresponded to relative reductions from baseline of 56.6% and 28.3%, respectively. After adjustment for baseline between-side BSA differences, the between-side difference was –4.0% (95% CI, –5.5% to –2.4%; P < .001).
"Ruxolitinib cream could represent a steroid-sparing, skin-directed alternative or second-line therapy," lead study author Alina Markova, MD, of the Dermatology Service at Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, and coauthors wrote.
Oral ruxolitinib (Jakafi) is approved for corticosteroid-refractory acute GVHD and cGVHD, and the topical formulation is approved for atopic dermatitis and nonsegmental vitiligo. Topical corticosteroids remain the mainstay of skin-directed therapy for cutaneous cGVHD, but their use is limited by adverse effects (AEs) such as skin atrophy, localized infections, and systemic complications with extensive use.
The trial, conducted at Memorial Sloan Kettering Cancer Center in New York, New York, enrolled patients 12 years of age or older with a history of allogeneic hematopoietic stem cell transplantation and clinically and/or histologically confirmed cutaneous cGVHD involving at least 2% BSA per National Institutes of Health consensus criteria.1,2 Patients with deep sclerotic cutaneous cGVHD were excluded.2
Patients were randomly assigned 1:1 to the body side (left or right) that received ruxolitinib 1.5% cream twice daily for 28 days; the contralateral lesional skin received placebo vehicle.1 Previous topical therapies were discontinued on day 0, and systemic GVHD therapy had to be stable for at least 4 weeks before enrollment. After day 28, patients could enter a 28-day open-label extension with ruxolitinib cream applied to both sides.
The primary end point was the absolute day-28 between-side difference in affected lesional BSA. Secondary end points included Physician's Global Assessment (PGA) and Composite Assessment of Index Lesion Severity (CAILS) scores at days 14 and 28, BSA at day 14, patient-reported outcomes, and safety.
Overall, 24 patients were randomly assigned between June 28, 2019, and September 8, 2022. The median age was 47.5 years (IQR, 32.5-67.5), 54% of patients were female, and 67% had an underlying acute leukemia. Patients had received a median of 2 (IQR, 1-2) prior systemic therapies for cGVHD, and 88% had previously received topical corticosteroids. Most patients (88%) had epidermal cGVHD; 3 patients had superficial lichen sclerosus–like disease. The median follow-up was 128 days (IQR, 90-280).
At day 14, among evaluable patients (n = 22), mean affected lesional BSA was 7.7% with ruxolitinib vs 10.4% with vehicle (P = .0020). Per PGA, clinical response on the ruxolitinib-treated side at day 28 occurred in 17 (74%) of 23 evaluable patients, including complete responses in 5 patients (22%) and partial responses in 12 patients (52%); the remaining 6 patients (26%) had no response or stable lesions.
Mean PGA scores were 2.7 (SD, 1.8) with ruxolitinib vs 3.8 (SD, 1.7) with vehicle at day 14 (P = .0020) and 1.9 (SD, 1.5) vs 3.7 (SD, 1.6) at day 28 (P = .0004). Mean CAILS scores were 6.9 (SD, 5.1) vs 11.0 (SD, 6.7) at day 14 (P = .0009) and 5.8 (SD, 4.9) vs 10.6 (SD, 6.8) at day 28 (P = .0040).
In a post hoc analysis, clinical response on the ruxolitinib-treated side occurred in all 7 patients who had prior exposure or refractoriness to oral ruxolitinib (n = 4) or were receiving concurrent systemic ruxolitinib (n = 3). Side-specific patient-reported outcomes did not show significant between-side differences.
Four patients (17%) experienced 5 treatment-emergent AEs of grade 2 or higher, including 2 serious AEs; per protocol, only AEs of grade 2 or higher were monitored and reported. All events were deemed unrelated or unlikely to be related to study treatment and included grade 2 cuticle fissures (n = 2; 8%), grade 3 sinusitis (n = 1; 4%), grade 3 lung infection (n = 1; 4%), and grade 5 central nervous system leukemia progression (n = 1; 4%), which occurred 6 months after trial treatment.
No treatment-related deaths occurred, and no treatment interruptions or dose modifications were required because of toxicity. No cases of skin atrophy, thinning, or increased bruising were reported.
