Belumosudil Plus Ruxolitinib Displays Activity in Steroid-Refractory/-Dependent cGVHD


Belumosudil plus ruxolitinib elicited responses with acceptable tolerability in patients with chronic graft-vs-host disease.

Hematology -

Hematology -

Belumosudil (Rezurock) plus ruxolitinib (Jakafi) displayed efficacy with a tolerable safety profile when used in the treatment of patients with steroid-refractory (SR) or steroid-dependent (SD) chronic graft-vs-host disease (cGVHD), according to findings from a retrospective study presented during the 2024 Transplantation & Cellular Therapy Meetings.

Out of 14 patients with advanced cGVHD, there was a 6-month overall response rate (ORR) of 71% (n = 10) including 2 patients with complete response (CR) and 8 with partial response (PR) at a median follow-up of 14 months. Belumosudil/ruxolitinib was also well tolerated, with no grade 3 or higher adverse events (AEs) except for 1 instance of pulmonary alveolar proteinosis (PAP) and persistent norovirus each.

Allogeneic hematopoietic cell transplant can often lead to cGVHD, which is the main cause of late non-relapse mortality. This is often treated upfront with systemic corticosteroids, but a majority of patients become refractory to this treatment and need to move on to the next treatment option. For patients with SR or SD cGVHD, therapies such as ruxolitinib, a JAK1/2 inhibitor, and belumosudil, a ROCK-2 inhibitor, are approved and often used sequentially.

“We hypothesize that treatment combination using drugs with distinct mechanism of action is safe and efficacious in advanced cGVHD,” the investigators wrote in their abstract. “Thus, we evaluated patients treated with combined belumosudil/ruxolitinib dual therapy at a single transplant center.”

In this retrospective review from Memorial Sloan Kettering Cancer Center, 14 patients with SR/SD cGVHD treated with belumosudil/ruxolitinib from September 2021 to October 2023 were included. These patients were assessed for treatment response at 6 and 12 months. Stable symptoms or progression of symptoms, treatment switch due to no response or benefit, or requirement for a higher dose of corticosteroids constituted treatment failure. Ruxolitinib was given at 5 mg to 10 mg twice daily and belumosudil was added to treatment for all patients except 1 who received belumosudil first and started ruxolitinib in addition after 6 months.

At 6 months, the ORR was 71% and stable disease rate was 29%; no patients had disease progression at this point. The investigators noted that all affected organs, such as gastrointestinal, lung, musculoskeletal, ocular, oral, and skin involvement in these patients showed some level of treatment response. An overall response at 12 months was seen in 7 out of the 10 evaluable patients; 1 patient had a CR and 6 had PR. There were 2 patients with stable disease and 1 had progressive disease.

There were no deaths at the time of treatment with belumosudil/ruxolitinib. The patient who experienced PAP recovered shortly after treatment discontinuation and the persistent norovirus was resolved using oral immunoglobulin treatment.

The median age for patients in the retrospective study was 47 years (range, 38-57). There were 8 male patients and 6 female patients. Eight patients had non-Hodgkin lymphoma (57%), 4 (29%) had acute leukemia, and 2 (14%) had myelodysplastic syndrome or myeloproliferative neoplasm. Five patients each had myeloablative conditioning and reduced intensity conditioning, and 4 had non-myeloablative conditioning. A majority of patients (71%) had a peripheral blood stem cell graft, and the rest received a cord blood graft (29%). Calcineurin inhibitor-based GVHD prophylaxis was given to all patients. Half of patients had moderate severity of their cGVHD, 4 had mild severity, and 3 had severe cGVHD.

“Our findings suggest that treatment combination with drugs that have a distinct mechanism of action is feasible and possibly synergistic. Nonetheless, a large prospective study is needed to determine the role of drug combination in cGVHD,” the investigators concluded.


Raju G, Walji M, Nemirovosky D, et al. Combined belumosudil-ruxolitinib therapy for the treatment of steroid-refractory chronic graft-versus-host disease (cGVHD) was associated with robust treatment response and was well-tolerated. Presented at: 2024 Transplantation and Cellular Therapies Meeting; San Antonio, TX; February 21-24, 2024. Abstract 375.

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