Belumosudil Combinations Show Promise in Steroid-Refractory cGVHD, Especially With Ruxolitinib

Combining belumosudil (BEL) with ruxolitinib (RUX) may offer improved clinical benefit for patients with steroid-refractory chronic graft-versus-host disease (SR-cGVHD) compared to standard combination therapies, according to an observational study published in Bone Marrow Transplantation.

“Following BEL’s FDA-approval, we noticed an increase in BEL combinations prescribed concurrently with the novel agent, RUX, at our institution,” explained Michelle Chin, University of Central Florida College of Medicine in Orlando, FL, USA. “We sought to investigate BEL’s use in combination with novel and standard agents,” they added.

The researchers aimed to evaluate the real-world use and outcomes of BEL combinations in adult SR-cGVHD patients following its US Food and Drug Administration (FDA) approval. They retrospectively analyzed the medical records of 26 patients treated with BEL combinations between July 2021 and July 2022. The cohort had a median age of 54 years and received a median of 3 prior lines of cGVHD therapy. Patients were divided into 2 groups: those treated with BEL plus standard agents (BEL+STD), such as prednisone or tacrolimus, and those treated with BEL plus ruxolitinib (BEL+RUX), a JAK1/2 inhibitor.

Thirteen patients received BEL+RUX, with BEL added a median of 10 months after starting ruxolitinib. Among 22 patients with skin involvement, most with advanced sclerotic features, BEL was primarily initiated due to disease progression or lack of improvement on prior regimens. The study found that mean overall response rates (ORRs) at 1 year were generally higher across most organ systems in the BEL+RUX group, although complete responses were not observed.

The median time to best response was 123 days, with partial responses and clinical benefits noted across the cohort. While 5 patients discontinued BEL due to lack of efficacy, survival outcomes were encouraging. The 24-month regimen overall survival (rOS) was 92% in the BEL+RUX group (95% CI, 79–100%) compared to 80% in the BEL+STD group (95% CI, 59–100%). Regimen nonrelapse mortality (rNRM) was lower in BEL+RUX (8%) versus BEL+STD (20%).

Infections were common, with 27 events reported, 40% of which were SARS-CoV-2 infections. There were 3 deaths: 2 from GVHD complications and 1 from COVID-19.

“In conclusion, our results suggest safety and possible efficacy of BEL+RUX combination therapy in treating refractory cGVHD,” concluded the study authors.

Reference

Chin MM, Tamaresis JS, Johnston LJ, et al. Belumosudil combination therapy for chronic graft-versus-host-disease in real-world clinical practice. Bone Marrow Transplant. 2025;60(3):393-395. doi:10.1038/s41409-024-02476-z