Low rates of chronic graft-versus-host disease with ruxolitinib maintenance following allogeneic HCT

Despite recent advances in graft-versus-host disease (GVHD) prophylaxis, novel approaches to effective prevention of chronic GVHD (cGVHD) remain of high importance. In this prospective, multicenter, phase 2 trial, ruxolitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, was administered as maintenance therapy after reduced-intensity allogeneic hematopoietic cell transplantation (HCT). GVHD prophylaxis consisted of tacrolimus and methotrexate. Ruxolitinib began between day +30 to 100 and was administered continuously in 28-day cycles for up to 24 cycles. Seventy-eight participants were enrolled before HCT; 63 participants received the intervention. The median start date of ruxolitinib after HCT was day +45. The most common grade ≥3 adverse events were neutropenia, thrombocytopenia, and anemia. Seven participants experienced grade ≥3 infectious events. GVHD-free, relapse-free survival at 1 year after HCT, the primary end point, was 70%. Grade 3 to 4 acute GVHD at 6 months was 4.8%, and moderate-severe cGVHD at 2 years was 16%. cGVHD requiring systemic therapy was 9.5% at 1 year and 13% at 2 years. Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT is associated with low rates of clinically significant cGVHD. The incorporation of JAK inhibition into GVHD prevention approaches warrants further investigation. This trial was registered at www.clinicaltrials.gov as #NCT03286530.