Efficacy and safety of belumosudil as compared with best available therapy for the treatment of cGVHD in the United States

作者：Kevin Hall, Aleksandr Lazaryan, Mark van der Laan, Catherine J. Lee, Aaron C. Logan, Susan Gruber, Shaum Kabadi, Irfan Khan, Charlie Nicholls, Lauren Rota, E. Nikaï, Ekaterina Ponomareva, Alexandra Koumas, Edmund K. Waller · 发表于：Blood Advances · 年份：2025 · DOI：10.1182/bloodadvances.2025015832 · 被引用次数：1 · 研究领域：Acute Lymphoblastic Leukemia research、Hematopoietic Stem Cell Transplantation、Chronic Myeloid Leukemia Treatments

ABSTRACT: Belumosudil was approved by the Food and Drug Administration in the United States for the treatment of relapsed/refractory chronic graft-versus-host disease (cGVHD) based on a randomized phase 2 trial comparing 2 belumosudil doses. The efficacy and safety of belumosudil vs the best available therapy (BAT) has not been studied. Applying rigorous statistical methodology to real-world data, this study estimated the efficacy of belumosudil vs BAT in cGVHD patients whose disease failed to respond to 2 to 5 prior lines of therapy (LOTs). Retrospective data between March 2015 and 2024 were collected across 8 US sites for 196 patients, contributing 113 belumosudil and 245 BAT LOTs. The primary outcome was 6-month overall response rate (ORR), defined as the proportion of complete or partial responses based on 2014 National Institutes of Health consensus criteria, physician assessment, or corticosteroid dose taper of ≥50% without cGVHD progression. Death, relapse, and beginning a new LOT were considered a lack of response. Targeted maximum likelihood estimation (TMLE) was used to estimate the 6-month ORR following belumosudil vs BAT (38.7% vs 26.8%, respectively) or 44.2% improvement with belumosudil (1-sided 95% confidence interval [CI], [4.4 to ∞]; P = .031). TMLE was also used to estimate 1-year failure-free survival when treated with belumosudil (61.2%) or BAT (47.8%), a 13.5% difference (95% CI, 1.5-100; P = .032). Descriptive assessment of safety showed adverse events r...