In a presentation at the 64th ASH Annual Meeting and Exposition, Franco Locatelli, MD, presented the first evidence reported in the phase 1/2 REACH4 trial on ruxolitinib added to corticosteroids (CS) in pediatric patients with grade 2-4 treatment-naïve or steroid-refractory (SR) acute graft-versus-host disease (aGVHD). Dr. Locatelli and colleagues identified a recommended phase 2 dose of 5 mg and 4 mg/m2 twice a day.
The REACH4 trial included 45 patients split into 4 treatment arms based on age (group 1, ≥12 to <18 years; group 2, ≥6 to <12 years; group 3, ≥2 to <6 years; group 4, ≥28 days to <2 years). Patients received ruxolitinib plus CS with or without a calcineurin inhibitor until week 24 or discontinuation. At baseline, 64.4%, 26.7%, and 8.9% of patients had grade 2, 3, and 4 aGVHD, respectively. Of those patients, 71.1% were SR and 28.9% were treatment naïve.
Ruxolitinib Treatment Comparably Effective in Pediatric Population
According to the authors, ruxolitinib exposure was comparable across all 4 age groups, and the starting doses of twice-daily 10 mg, 5 mg, and 4 mg/m2 in groups 1, 2, and 3, respectively, were selected as the recommended phase 2 dose. Dr. Locatelli noted that the recommended dose had not yet been determined for the group 4 age range.
Preliminary efficacy analysis found an objective response rate (ORR) for all patients of 84.4% (n=38) at day 28, with a durable ORR of 66.7% (n=30) at day 56. In subgroup analyses, treatment-naïve patients had a day-28 ORR of 69.2% and a day-56 durable ORR of 61.5%, while SR patients had rates of 90.6% and 68.8%, respectively.
A total of 38 (84.4%) patients required at least 1 dose adjustment or interruption, most commonly due to adverse events (51.1%), dose tapering per study protocol (44.4%), and per-protocol dose change or interruption (31.1%). The authors noted that no new safety signals were observed, and adverse events were similar to previous ruxolitinib trials.
The authors summarized that ruxolitinib treatment had high ORRs in a pediatric SR aGVHD population, which were comparable to previously published findings, and an as-expected safety profile.
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