Heidenreich Silke, Egger-Heidrich Katharina, Halter Jörg P, Jost Lasse, Stölzel Friedrich, Perl Markus, Denk Alexander, Edinger Matthias, Herr Wolfgang, Kröger Nicolaus, Wolff Daniel, Ayuk Francis, Fante Matthias A
Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Department of Internal Medicine I, University Hospital Carl Gustav Carus, Dresden, Germany.
Bone Marrow Transplant. 2025 Apr;60(4):439-446. doi: 10.1038/s41409-024-02507-9. Epub 2025 Jan 14.
Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval. The patient cohort had a long history of cGvHD (median 44 months) and was heavily pretreated (median 4 prior lines). The overall response rate was 42% (95%CI, 25-60%) including organ responses in all organs except the liver (n = 2). The median time to response was 3 months (range, 1-9 months) and 8 of 14 patients (57%) had a durable response at last follow-up. One-third of patients had at least a 50% reduction in concomitant corticosteroid dosage. Median failure-free survival and median overall survival were 16.5 and 23.1 months, respectively. Adverse events ≥CTCAE grade 3 were reported in 27% of patients, with a predominance of infectious events, including one fatal course. The results are consistent with previous prospective trials including a favorable safety profile, while acknowledging the challenges of a heavily pretreated patient cohort.
贝拉莫司他是一种一流的ROCK2抑制剂，已获美国食品药品监督管理局（FDA）批准用于三线治疗慢性移植物抗宿主病（cGvHD）。在这项回顾性真实世界分析中，我们报告了来自5个德国/瑞士移植中心的贝拉莫司他治疗的安全性和有效性数据。由于缺乏欧洲药品管理局（EMA）的批准，共有33例成年患者（中位年龄59岁）因个人要求接受了中度（n = 2）或重度（n = 31）cGvHD的治疗。该患者队列有较长的cGvHD病史（中位44个月），且接受过大量预处理（中位4线治疗）。总体缓解率为42%（95%CI，25 - 60%），包括除肝脏外所有器官的器官缓解（n = 2）。中位缓解时间为3个月（范围1 - 9个月），14例患者中有8例（57%）在最后一次随访时获得持久缓解。三分之一的患者伴随使用的皮质类固醇剂量至少减少了50%。中位无失败生存期和中位总生存期分别为16.5个月和23.1个月。27%的患者报告了≥3级的不良事件，主要是感染性事件，包括1例死亡病例。结果与之前的前瞻性试验一致，包括良好的安全性，同时也认识到了一个接受过大量预处理的患者队列所面临的挑战。
