August 15, 2025

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

Key Points

Ruxolitinib administration resulted in a 71% one-year graft-versus-host disease-free survival for patients with myelofibrosis after transplantation.
During a median follow-up of 27 months, the overall survival rate was 82% with notable low rates of severe acute graft-versus-host disease.
This was a phase II, multicenter clinical trial involving 43 participants receiving reduced-intensity hematopoietic cell transplantation.
The findings highlight the safety and tolerability of ruxolitinib, suggesting it may improve survival outcomes and reduce the risk of complications post-transplant.

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.

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