Acalabrutinib for treatment of steroid-refractory chronic graft vs. host disease.

Novel therapies are needed in steroid-refractory chronic graft vs. host disease (SR-cGVHD). We tested acalabrutinib for SR-cGVHD in a multicenter phase II trial (NCT04198922). The primary endpoint was NIH best overall response rate (ORR, comprised of complete (CR) and partial (PR) responses). Secondary endpoints were safety, duration of treatment response, patient-reported outcomes, and failure-free survival (FFS). Included subjects (N=50) were age ≥ 18 with active NIH moderate-severe cGVHD despite prior steroid therapy. Acalabrutinib was given at 100mg orally twice daily for 28 day cycles with intent to complete at least 6 treatment cycles. Responding patients could continue through 24 cycles. Median time from cGVHD diagnosis to enrollment was 31.6 months (IQR 10.1-49.6 months). Participants had received a median of three prior lines of systemic cGVHD therapy including prior ruxolitinib (56%) and belumosudil (48%). Best ORR of all participants was 62% (95% CI 47-75%) by 6 months, and responders showed median duration of response of 28 weeks. Best ORR in those completing at least one cycle of therapy (45 subjects) was 69% (95% CI 53-82%). FFS of the entire population was 59% at 6 months, and 38% at 1 year. Discontinuation of acalabrutinib for toxicity within 6 cycles occurred in 18% of subjects. A total of 27% of subjects demonstrated clinically meaningful improvements in Lee Symptom Scale summary score, and this was not significantly different between responders vs. non-responders. Primary results from this phase II trial demonstrate activity of acalabrutinib in SR-cGVHD.