ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease
Phase IIa, open-label, dose-finding study (n=54) reports high overall response rate after a median follow-up of 29 months (65%, 69% and 62% for belumosudil 200 mg once daily, 200 mg twice daily, and 400 mg once daily, respectively), with a median duration of response of 35 weeks.
Source:
Journal of Clinical Oncology
SPS commentary:
Authors report treatment was well tolerated with low rates of cytopoenia and no unexpected adverse events or increased risk of infection including cytomegalovirus infection and reactivation.
A related editorial discusses this research, stating that the new molecularly targeted therapies for the treatment of chronic graft vs host disease (cGVHD) herald the dawn of a new age. Historically, the treatment of cGVHD has relied on potent anti-inflammatory agents such as corticosteroids or immunosuppressive agents largely directed against T cells. With a deeper understanding of the pathophysiology of cGVHD, novel therapeutic targets and strategies have emerged, targeting not only the inflammatory components of cGVHD but also the fibrotic sequelae. Some of these strategies are currently being tested in clinical trials of fibrosing diseases, where disease manifestations are similar to those found in cGVHD or in cGVHD itself. The future use of these targeted agents, including ROCK2 inhibitors, in established cGVHD will target the fibrotic organ manifestations of disease such as bronchiolitis obliterans, whereas earlier use in patients with cGVHD could treat the early inflammatory finding of the disease, while preventing the long-term development of fibrosis, leading to marked improvements in quality of life for hematopoietic stem-cell transplant recipients.