Onkologie Erding, Bajuwarenstr.3, Erding, Germany.
Department of Medicine III, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Ann Hematol. 2024 Oct;103(10):4065-4077. doi: 10.1007/s00277-024-05908-4. Epub 2024 Jul 29.
Recurrent problems of patients with myelofibrosis (MF) are cytopenias, debiliating disease-related symptoms and splenomegaly. Whereas the latter are usually addressed by the JAK1/2 inhibitors ruxolitinib and fedratinib, cytopenias often remain critical. Momelotinib, a JAK1/2 inhibitor recently approved for the treatment of anemic MF patients, was shown to improve anemia via a direct inhibition of activin A receptor type I. In this German-wide, multicenter, retrospective analysis the safety and efficacy profile of momelotinib was evaluated in a real world setting within a cohort of 60 MF patients independent of pre-treatment. The median duration of treatment was 12 weeks. As a new, but manageable safety finding, creatinine increase (CTC°1-2) was detected in 10/60 patients (17%). Interestingly, not only hemoglobin levels increased in 84% of patients, but also platelet values (67%). In the cohort of transfusion-dependent individuals (n = 38), transfusion requirement improved in 15 patients (39%) with 8 reaching transfusion independency (21%). Transfusion independency was achieved within a median of 4 weeks (range 2-12). Spleen size decreased in 13/53 individuals (25%) with a median response time of 6 weeks. Thereof, 11 patients had been pre-treated with JAK inhibitor(s) (85%). Clinical improvement was detected in 24/51 symptomatic individuals (47%) with a median response time of 4 weeks. 5 patients stopped treatment due to side effects (8%), 6 patients due to a worsening of clinical symptoms (10%). Taken together, the MoReLife analysis identifies momelotinib as potent and safe therapeutic option also for heavily pre-treated cytopenic MF patients under real world conditions.
骨髓纤维化(MF)患者常出现细胞减少、进行性疾病相关症状和脾肿大等问题。虽然 JAK1/2 抑制剂芦可替尼和 fedratinib 通常可用于治疗后两者,但细胞减少症往往仍是关键问题。Momelotinib 是一种最近被批准用于治疗贫血性 MF 患者的 JAK1/2 抑制剂,其通过直接抑制激活素 A 受体 I 型来改善贫血。在这项德国多中心回顾性分析中,在 60 例 MF 患者队列中评估了 momelotinib 的安全性和疗效概况,该队列独立于预处理。治疗的中位持续时间为 12 周。作为一个新的但可管理的安全性发现,10/60 例患者(17%)检测到肌酐升高(CTC°1-2)。有趣的是,不仅 84%的患者血红蛋白水平升高,血小板值也升高(67%)。在依赖输血的患者队列(n=38)中,15 例患者(39%)的输血需求得到改善,其中 8 例达到输血独立性(21%)。输血独立性在中位数 4 周(范围 2-12)内达到。53 例中有 13 例(25%)的脾脏大小缩小,中位反应时间为 6 周。其中 11 例曾接受过 JAK 抑制剂(85%)治疗。在 51 例有症状的患者中,24 例(47%)出现临床改善,中位反应时间为 4 周。由于副作用(8%),5 例患者停止治疗,6 例患者因临床症状恶化(10%)停止治疗。总之,MoReLife 分析表明,在现实世界条件下,对于大量预处理的细胞减少性 MF 患者,Momelotinib 是一种有效且安全的治疗选择。