Work

Phase II Study of Peri- and Post-Transplant Ruxolitinib for Patients With Myelofibrosis Receiving Allogeneic Hematopoietic Cell Transplantation

Year: 2025

Type: article

Abstract: PURPOSE We conducted a phase II, multicenter trial (ClinicalTrials.gov identifier: NCT03427866 ) investigating ruxolitinib administration before, during, and after allogeneic hematopoietic cell transplantation (HCT) for patients with primary or secondary myelofibrosis (MF). The primary end point was 1-year graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). METHODS Between 2018 and 2023, 43 participants received reduced-intensity HCT from 7/8 or 8/8 human leukocyte antigen–matched donors, with use of tacrolimus and methotrexate as GVHD prophylaxis. Participants were treated with ruxolitinib 5 mg twice a day starting on Day –14, and continued ruxolitinib until 1 year after transplant. Most participants (n = 36, 84%) had Dynamic International Prognosis Scoring System plus intermediate-2/high-risk MF and 26 (60%) were receiving ruxolitinib before HCT. Common molecular mutations before transplant included Janus kinase 2 (n = 25), CALR (n = 8), MPL (n = 5), and ASXL1 (n = 13). RESULTS With a median follow-up of 27 months (range 1-64), 1-year GRFS was 71%. Overall survival (OS), progression-free survival, and cumulative incidence of nonrelapse mortality and disease relapse at 2 years were 82%, 72%, 12%, and 16%, respectively. The cumulative incidence of grade 3 to 4 acute GVHD at 6 months was 2.4%. Two-year moderate/severe chronic GVHD was 15%. The most common severe (grade ≥3) adverse events were hematologic in nature. In univariable analysis, spleen >20 cm before HCT (hazard ratio, 5.11, P = .04) was associated with worse OS (2-year OS: 67% v 89%, P = .015). CONCLUSION In summary, continued ruxolitinib administration during and after HCT demonstrates safety and tolerability, and is associated with low rates of clinically significant GVHD and encouraging survival outcomes for MF.

Source: JCO oncology advances.

DOI: 10.1200/oa-25-00020