Belumosudil combination therapy in a real-world setting “appears safe, tolerable, and effective” in patients with established, refractory chronic graft-versus-host disease (GVHD), according to research presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition.
Michelle Chin, MS, of the University of Central Florida College of Medicine, and colleagues conducted the study because belumosudil, ibrutinib, and ruxolitinib are approved by the U.S. Food and Drug Administration (FDA) for use in patients with chronic GVHD who received 1-2 or more lines of previous therapy.
“Encouraging overall response rates have been reported for all 3 agents; however, complete responses are rare and there are still a large number of patients who do not respond or lose the response over time,” Ms. Chin and colleagues wrote. “One of the approaches to overcome potential resistance to single agent use is to combine the new agents with each other or with other therapies … as there can be synergy across agents with different mechanisms of action.”
The researchers gathered data from Stanford’s real-world practice of using belumosudil, a ROCK2 inhibitor, in combination with other therapies since its FDA approval in July 2021. They conducted a retrospective chart review of 26 patients who received belumosudil in combination with other treatments at the Stanford Cancer Institute from July 2021 to July 2022.
Skin, which was affected in 20 patients, was the most frequently affected organ, with the mouth affected in 19 patients, the eyes in 15 patients, and joints/fascia in 15 patients.
Patients received a median of 3 prior lines of therapy before starting belumosudil treatment. The combination therapies used with belumosudil included several combinations of 3-4 drugs with concurrent use of ruxolitinib, extracorporeal photopheresis, prednisone, sirolimus, or a calcineurin inhibitor. In the cases that belumosudil was combined with ruxolitinib, belumosudil was considered the add-on drug.
The researchers assessed the responses based on organ symptom scoring and global rating by clinician assessment per the 2014 National Institutes of Health Consensus Criteria. The median follow-up was 213.5 days after belumosudil initiation.
More than three-quarters of patients had a response following the addition of belumosudil, with an overall response rate of 77%. Most patients (85%) who had skin involvement showed a response, 53% with joint/fascia involvement had responses, and 33% with eye involvement had responses.
Lower response rates were seen in patients with lung involvement, who had a 30% response rate; in patients with liver involvement, who had a 13% response rate; and in patients with mouth involvement, who had an 11% response rate. None of the patients with lower-tract gastrointestinal involvement had responses.
“No clinically evident adverse drug reactions occurred in the belumosudil combinations, although variable dosing of the combined agents was used with the approved belumosudil dose of 200 mg [orally] daily,” the study’s authors wrote.
The researchers reported infectious adverse events “consistent with the immunosuppressive effects of [chronic] GVHD therapies” in 42% of patients. The most common infectious adverse event, occurring in 36% of patients who had an infectious adverse event, was SARS-CoV2 infection. A total of 29% had cytomegalovirus reactivation, 21% had a bacterial infection, 7% had a rhinovirus infection, and 7% had a respiratory syncytial virus.
“The number of infection events with the new agent combination of belumosudil plus ruxolitinib was reviewed separately and was not increased over the other belumosudil combinations,” the researchers wrote.
No deaths occurred in the group of 26 patients.
“In our institutional practice, administration of belumosudil in combination therapy appears safe, tolerable, and effective in patients with established, refractory [chronic] GVHD,” the researchers concluded. “The results of our retrospective study highlight the feasibility of the next phase of belumosudil research for combination therapy in this difficult-to-treat population.”
Chin M, Shizuru JA, Muffly L, et al. Belumosudil combination therapy in refractory chronic graft-versus-host disease. Abstract #2090. Presented at the 64th American Society of Hematology Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.