Belumosudil, a selective inhibitor of rho-associated coiled-coil-containing protein kinase 2 (ROCK2), is increasingly used in treating chronic graft-versus-host disease (cGVHD), particularly in patients who have undergone multiple prior lines of therapy. Real-world data and recent studies highlight its potential as a valuable option for managing this challenging condition. A recent retrospective study evaluating the efficacy and safety of belumosudil in a cohort of patients from German and Swiss transplant centers provides further insights into its clinical application.
Belumosudil Usage Patterns in cGVHD Treatment
Analysis of real-world treatment patterns indicates that belumosudil is commonly administered in combination with other agents and after patients have failed three or more prior lines of therapy. A study utilizing data from the Komodo Healthcare Map, which included patients with evidence of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and cGVHD, revealed that the median starting dose of belumosudil was 200 mg per day. Approximately 30.4% of patients received a twice-daily (BID) dose at the index date, with 31.6% receiving BID dosing at any time during the study. The median time from cGVHD diagnosis to initiation of belumosudil treatment was 489 days, often in later lines of therapy.
Efficacy and Safety in Advanced cGVHD
A multicenter, retrospective observational study conducted across five German and Swiss transplant centers (Regensburg, Hamburg, Kiel, Dresden, Basel) analyzed 33 adult patients with persistent cGVHD treated with belumosudil. The study, published in Nature, included patients who had received a median of four prior lines of systemic treatment. At the time of belumosudil initiation, 94% of patients had severe cGVHD, with a median of three organs involved. The best overall response rate (ORR) was 42%, with complete organ remissions observed in manifestations affecting the mouth (33%), eyes (29%), GI tract (67%), fascia (25%), and lungs (23%).
The median time to response (TTR) was three months, and the median duration of response (DOR) was six months. A subjective response, assessed by physician evaluation or patient report, was observed in 73% of patients. Furthermore, steroid dose reduction was achieved in 14 of 22 patients, with a median best reduction of 50%. The failure-free survival (FFS) rates at 6 and 12 months were 76% and 64%, respectively, while overall survival (OS) rates were 96% and 88% at the same time points.
Tolerability and Adverse Events
Belumosudil demonstrated a manageable safety profile. Treatment-emergent adverse events (TE-AE) of grade 3 or higher occurred in 27% of patients, with infectious events being the most common. Two patients discontinued treatment due to adverse events, and one patient died while undergoing treatment, likely due to a pulmonary infection.
Implications for Clinical Practice
The findings from these studies suggest that belumosudil is a valuable treatment option for patients with cGVHD, particularly those who have failed multiple prior therapies. The real-world data indicate that it is often used in combination with other agents, while the retrospective study demonstrates its efficacy in patients with advanced disease. The steroid-sparing effect and manageable safety profile further support its use in clinical practice.
Future Directions
Ongoing and future clinical trials are expected to provide additional data on the safety and efficacy of belumosudil in specific patient populations with cGVHD. These include studies evaluating its use in first-line therapy, in combination with steroids or rituximab, and in patients with new-onset bronchiolitis obliterans syndrome. These investigations will further refine the role of belumosudil in the treatment landscape of cGVHD.
