Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic hematopoietic cell transplantation, leading to morbidity, mortality, and impaired quality of life. The rho-associated coiled-coil–containing protein kinase-2 (ROCK2) signaling pathway plays a crucial role in the Th17/regulatory T cells balance and profibrotic pathways, making it a potential target for cGVHD treatment.
A phase IIa, open-label, dose-finding study evaluated the safety and efficacy of belumosudil (KD025), a selective ROCK2 inhibitor, in 54 patients with cGVHD who had received one to three prior lines of therapy. The primary endpoint was the overall response rate (ORR), with secondary endpoints including duration of response, quality-of-life improvements, and corticosteroid (CS) dose reductions.
Results showed an ORR of 65% to 69% across different dosing regimens, with a median duration of response of 35 weeks. Significant improvements in quality of life and reductions in CS doses were observed, with 19% of patients discontinuing CS treatment. The 2-year overall survival rate was 82%, and the treatment was well-tolerated with low rates of cytopenia and no unexpected adverse events.
Belumosudil's efficacy in inducing responses, coupled with its safety profile, suggests it as a promising therapeutic option for patients with treatment-refractory cGVHD. The study's findings support further investigation into belumosudil's role in managing cGVHD, highlighting its potential to improve patient outcomes significantly.
