Belumosudil for Chronic Graft-Versus-Host Disease after 2 or More Prior Lines of Systemic Therapy: 3-Year Follow-up of the Rockstar Study

Belumosudil is an oral selective rho-associated coiled-coil–containing protein kinase-2 inhibitor approved for the treatment of chronic graft-versus-host disease (cGVHD) following an allogeneic hematopoietic cell transplant. In the pivotal ROCKstar study (NCT03640481), with results first reported in 2020, patients on belumosudil 200 mg QD and 200 mg BID achieved best ORRs of 74% and 77%, respectively, with a median follow-up of 14 months. Belumosudil was well tolerated and had AEs consistent with those expected in patients with cGVHD receiving corticosteroid (CS) therapy and other immunosuppressive therapies. Here we report the 3-year follow-up results from the ROCKstar study. This follow-up of the pivotal ROCKstar study evaluated belumosudil 200 mg QD (n=77) and BID (n=75) in 152 participants with cGVHD (aged 21-77 years) who received 2 to 5 prior lines of systemic therapy (LOTs), including 20 unreported participants enrolled in a subsequent biomarker study. At baseline, the median age of patients was 55 years, median time from diagnosis to enrollment was 28 months, median prednisone-equivalent dose of CS was 0.19 mg/kg/d, 70% of patients had severe cGVHD, 52% had ≥4 organs involved, 49% had received >3 prior LOTs (including ibrutinib [35%] or ruxolitinib [36%]) and 73% were refractory to their last LOT. The 3-year ORR in the modified intent-to-treat (mITT, defined as randomized patients who received ≥1 dose of belumosudil) population was 74% and 76% in the 200 mg-QD and 200 mg-BID arms, respectively. With the increased sample size of patients exposed to belumosudil, the ORR remained stable. The ORR and responses observed across all organ systems were consistent with the primary analysis. The overall 2-year and 3-year FFS rates were 48.0% and 44.1%, respectively. Among responders, the subsequent overall 2-year and 3-year FFS rates were 57.0% and 51.8%, respectively. The incidence rates for each safety event remained stable, and no new treatment-related AEs occurred. In the mITT population, 8% and 7% of patients in the 200-mg QD and 200-mg BID arms, respectively, have remained on therapy for ≥36 months, and 23.4% and 25.3% of patients successfully stopped all immunosuppressants. Overall, 21.0% and 13.2% of patients discontinued treatment due to cGVHD progression and AEs, respectively. There was a decrease in discontinuation rates due to AEs and progression of cGVHD each year after follow-up. In this 3-year follow-up study, patients continued to show a good response to belumosudil with no new safety concerns. FFS was 44.1% (41.6% in the 200-mg QD arm and 46.7% in the 200-mg BID arm) at 3 years for all patients and 51.8% (49.1% in the 200-mg QD arm and 54.4% in the 200-mg BID arm) for responders, showing good control of cGVHD and long-term tolerability.