ROCK2 Inhibitor Belumosudil for Chronic Graft-vs-Host Disease

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In a phase IIa study reported in the Journal of Clinical Oncology, Jagasia et al found that the oral ROCK2 inhibitor belumosudil produced high response rates and reduced corticosteroid use among patients with chronic graft-vs-host disease after allogeneic bone marrow or hematopoietic cell transplantation for hematologic malignancy.  

As stated by the investigators, “The rho-associated coiled-coil–containing protein kinase-2 (ROCK2) signaling pathway regulates the Th17/regulatory T cells balance and controls profibrotic pathways. Selective ROCK2 inhibition with belumosudil may offer a novel approach to the management of [chronic graft-vs-host disease].”

Study Details

In the U.S. multicenter trial, 54 patients were enrolled in sequential dosing cohorts between September 2016 and March 2018, with 17 receiving belumosudil at 200 mg once daily, 18 at 200 mg twice daily, and 21 at 400 mg once daily. Belumosudil was continued until chronic graft-vs-host disease progression or unacceptable toxicity. All patients were receiving corticosteroid treatment. Overall, 78% of patients had severe chronic graft-vs-host disease; 50% had four or more organs involved; 73% had chronic graft-vs-host disease refractory to their last line of therapy; and all patients had received one or more prior systemic line of therapy for chronic graft-vs-host disease, with 70% having received two or more prior lines.

The primary endpoint was overall response rate on 2014 National Institutes of Health Chronic Graft-vs-Host Disease Consensus Criteria.


Median follow-up was 29 months. The overall response rate was 65%, with rates of 65%, 69%, and 62% at doses of 200 mg once daily, 200 mg twice daily, and 400 mg once daily. Response was observed in 60% of 42 patients with severe chronic graft-vs-host disease, 66% of 35 who had received two or more prior lines of therapy, 63% of 35 who were refractory to their last line of therapy, and 70% of 27 in patients with involvement of four or more organs. Median duration of response was 35 weeks.


  • The overall response rate was 65%.
  • Response was observed in 60% of patients with severe chronic graft-vs-host disease and 70% of patients with involvement of four or more organs.

Quality of life was assessed by the Lee Symptom Scale, with a decrease of ≥ 7 points defined as clinically meaningful. Clinically meaningful improvement was observed in 50% of patients. A reduction corticosteroid dose was observed in 67% of patients (mean dose reduction of 45%), with 19% completely discontinuing corticosteroid treatment.

The failure-free survival rate was 76% and 47% at 6 and 12 months. The 2-year overall survival rate was 82%.

Adverse Events

Grade ≥ 3 adverse events occurred in 61% of patients, with the most common being dyspnea (13%), increased liver function tests (7%), hyperglycemia (7%), and hypoxia (7%). Serious adverse events occurred in 43%, with the most common being dyspnea (7%), lung infection (6%), hypoxia (4%), and influenza-like illness (4%). Grade ≥ 3 cytopenias were reported in two patients (4%). No cases of cytomegalovirus infection or reactivation were reported. Three patients discontinued treatment due to treatment-related adverse events, consisting of diarrhea, headache, and fatigue. No treatment-related deaths were reported.

The investigators concluded, “Belumosudil treatment resulted in a high overall response rate and overall survival rate and demonstrated quality-of-life improvements, corticosteroid dose reductions, and limited toxicity. Data from the study indicated that belumosudil may prove to be an effective therapy for patients with treatment-refractory [chronic graft-vs-host disease].”

Aleksandr Lazaryan, MD, MPH, PhD, of Moffitt Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Kadmon Corporation, LLC. For full disclosures of the study authors, visit

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