Efficacy and safety of belumosudil for treatment of cGVHD: multicenter retrospective analysis of the French cohort of the compassionate use program, on behalf of the French Society of Bone Marrow Transplantation and Cellular Therapy

Abstract

Chronic graft versus host disease is a major cause of morbidity after allogeneic haematopoietic cell transplantation. Belumosudil has recently been approved for the treatment of cGVHD refractory after two lines of treatment. However, few data are available to evaluate its efficacy and safety in real life. 68 patients with cGVHD received belumosudil through a compassionate access program in France. The median follow-up was 337 days from belumosudil initiation. Eighty-two percent of patients had severe cGVHD with a median of three organs involved. Patients had received a median of three prior treatment lines. Median treatment duration was 251 days. The best overall response rate (ORR) was 57.3%, including 14.7% complete remission (CR) and 42.6% partial response (PR). The ORR at three and six months was 47% and 45.6%, respectively. Liver and mouth involvement showed the highest response rates (72.7% and 70.4%), while lung involvement had the lowest (17.2%). Median failure-free survival (FFS) was not reached, with 6- and 12-month FFS rates of 89.1% and 80.4%, respectively. Nine patients died, mainly from GVHD (n = 5). Ten adverse events were reported, leading to treatment discontinuation in three cases. These results support the efficacy and safety of belumosudil in refractory cGVHD.

Fig. 1. Outcome and response to belumosudil.

a Overall survival from belumosudil onset (OS). b Failure-free survival (FFS) for the entire cohort (n = 68) with a median follow-up of 337 days. c FFS for patients receiving belumosudil as a third-line therapy (yellow) or after 3 lines of treatment (blue). Statistical analyses were performed at one year using a log-rank test and a significance defined for p < 0.05. d Stacked histogram with response to belumosudil at 3 months, 6 months and best response during follow-up. e Sankey diagram depicting the evolution of cGVHD grading according to NIH criteria, at GVHD onset, belumosudil onset, 3 months and 6 months. f Sankey diagram illustrating the evolution of response at 3 and 6 months, according to initial cGVHD grading at diagnosis and belumosudil onset. g Stacked diagram with best response per organ.