Itacitinib plus calcineurin inhibitor-based therapy for prophylaxis of graft-versus-host disease: GRAVITAS-119 results.

GRAVITAS-119 (NCT03320642), a single-arm, open-label, phase 1, proof-of-concept study, assessed addition of itacitinib to standard-of-care graft-versus-host disease (GVHD) prophylaxis regimens in reduced-intensity conditioning peripheral blood allogeneic hematopoietic stem cell transplant. Day 28 hematologic recovery (percentage of patients demonstrating neutrophil recovery and platelet recovery) was the primary endpoint. Of 84 enrolled patients, 41 received itacitinib plus tacrolimus/methotrexate (nine with antithymocyte globulin [ATG]), 24 received itacitinib plus cyclosporine A/mycophenolate mofetil (16 with ATG), and 19 received itacitinib plus post-transplant cyclophosphamide/tacrolimus. Hematologic recovery was achieved by 51/55 (92.7%) evaluable patients (neutrophil recovery, 98.7%; platelet recovery, 94.6%). Estimated 1-year GVHD-free, relapse-free survival was 39.7%; estimated 1-year overall survival was 78.3%. Cumulative incidences for grade 2-4 and grade 3-4 acute GVHD at Day 180 were 13.2% and 4.8%, respectively; cumulative incidence of chronic GVHD at 1 year was 37.8%. Most common grade ≥ 3 adverse events were cytopenias; grade ≥ 3 infections occurred in 23 (27.4%) patients. Most patients receiving itacitinib plus standard-of-care GVHD prophylaxis achieved hematologic recovery, with any-grade GVHD and infection rates similar to previous reports with standard-of-care prophylaxis. Addition of itacitinib to GVHD prophylaxis permits timely hematologic recovery and does not increase GVHD or infection rates, although unmet need still remains for improved regimens.