Line-of-therapy stratified efficacy of belumosudil in cgvhd : Real-world evidence Free

Background: In China, belumosudil has been approved for patients failing ≥1 prior therapy, yet dedicated evidence supporting its second-line efficacy remains limited. We describe real-world outcomes of belumosudil in cGVHD patients, including presenting the dedicated analysis focusing on its second-line efficacy.

Methods: This study retrospectively collected baseline characteristics, treatment and clinical outcomes of allo-HSCT recipients diagnosed with cGVHD, who received belumosudil at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between January 1, 2024, and March 31, 2025. Patients were stratified by lines of therapy (LOT) : 1 prior LOT vs. ≥2 prior LOTs. The primary outcome was overall response rate (ORR), defined as the proportion of patients who achieved either a complete response (CR) or partial response (PR) per the 2014 NIH criteria. Secondary outcomes included 3 month-ORR, organ-specific responses, time to response (TTR), corticosteroid dose reductions, failure-free survival (FFS), and safety.

Results: A total of 24 cGVHD patients were included, with a median age of 32.5 years (range: 15, 60) and predominantly male (70.8%). The majority of basline characteristic were comparable between patients with 1 prior line of therapy (LOT) (n=15) and those with ≥2 prior LOTs (n=9), including conditioning regimens (all P>0.05), and prior acute GVHD (46.7% vs. 55.6%, P=0.999). However, donors were significantly younger for patients with one prior LOT (31.1 vs. 42.6 years, P=0.036), while prior JAK inhibitor use was more frequent in those with ≥2 prior LOTs (88.9% vs. 26.7%, P=0.009) with numerically higher proportion of haploidentical donor (77.8% vs. 46.7%, P=0.357). Prior to belumosudil treatment, the ≥2 prior LOTs group had numerically higher severe cGVHD rates (33.3% vs. 20.0%, P=0.635) and more organs involved (median 3 vs. 2, P=0.782). Organ involvement patterns were comparable.

For concomitant treatments, cyclosporine was more frequent in patients with 1 prior LOT (73.3% vs. 22.2%, P=0.033), whereas tacrolimus was more common in patients with ≥2 prior LOTs (13.3% vs. 66.7%, P=0.021). No statistically significant differences were observed for other concomitant treatments, including corticosteroid (73.3% vs. 33.3%, P=0.092), mycophenolate mofetil (80.0% vs. 66.7%, P=0.635) and JAK inhibitor (33.3% vs. 44.4%, P=0.678).

At a median follow-up of 127.5 days (IQR 98.3–156.7), the overall population achieved an ORR of 95.8% (95% confidence interval [CI], 78.9-99.9). The prespecified line-stratified comparison demonstrates a numerically higher ORR in second-line therapy (100% [15/15] vs 88.9% [8/9]), P=0.375). The 3-month ORR was 90.0% (18/20) in the overall cohort, with 91.7% (11/12) in 1 prior LOT versus 87.5% (7/8) in ≥2 prior LOTs (P>0.999). The 1 prior LOT group yielded 100.0% ORR (15/15) compared to 88.9% (8/9) for ≥2 prior LOTs. In the organ-specific analysis, we observed a higher ORR in the 1 prior LOT, except in the eyes (50% vs. 60%). Notably, among 5 patients with lung involvement, ORR was 100% (2/2) in 1 prior LOT vs. 0% (0/3) in ≥2 prior LOTs. The median TTR was 21 days (21 days vs. 31 days for 1 vs. ≥2 prior LOTs), and 41.7% of patients reduced corticosteroid dosing. Median FFS was not reached in either group, with one non-relapse death (cause undetermined). No grade ≥ 3 adverse events (AEs) or dose reductions occurred.

Conclusion: In this real-world analysis dedicated to pretreated cGVHD, belumosudil achieved 95.8% (23/24) ORR in overall cohort, with 100% ORR specifically in second-line therapy (15/15). The 88.9% ORR in patients with ≥2 prior LOTs (8/9), 41.7% steroid reduction, and no grade≥3 AEs support its prioritization for early second-line use.