Work

The safety and efficacy of belumosudil and ruxolitinib combination in ruxolitinib refractory cGVHD

Year: 2026

Type: article

Abstract: Despite advances with JAK and ROCK inhibitors, durable responses in chronic GVHD (cGVHD) remain challenging. For patients with advanced, multi-refractory disease, simultaneously targeting multiple pathways may be necessary. Building on preclinical synergy between JAK and ROCK inhibition, we evaluated the combination of belumosudil and ruxolitinib in a multicenter, retrospective study of 57 ruxolitinib-refractory cGVHD patients. The cohort had high-risk features, with 63.2% having severe NIH-grade disease and 66.7% receiving ≥ 5 prior lines of therapy.The primary endpoint was the 3-month overall response rate (ORR). At a median follow-up of 170 days, the ORR was 59.6%, with a best overall response of 75.4%. Notably, in patients with lung involvement (63.2%), 83.3% achieved symptom-based responses, versus 3.7% FEV1 improvement. The 12-month failure-free survival rate was 94.5%, and 86.4% of patients achieved a corticosteroid reduction. The regimen demonstrated a favorable safety profile, with only 5.3% grade ≥ 3 pneumonia and no treatment-related discontinuations or severe hematologic toxicities.These results confirm the clinically meaningful efficacy and safety of dual JAK/ROCK inhibition in this heavily pretreated population. These findings support the mechanistic rationale for concurrent pathway inhibition and warrant prospective validation in randomized controlled trials.

Source: Bone Marrow Transplantation

DOI: 10.1038/s41409-026-02848-7