Al-Ali Haifa Kathrin, Gerds Aaron T, Grunwald Michael R, Yu Jingbo
University Hospital Halle, Halle (Saale), Germany.
Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
Clin Lymphoma Myeloma Leuk. 2025 May;25(5):e262-e281. doi: 10.1016/j.clml.2024.12.013. Epub 2024 Dec 27.
Myelofibrosis (MF) is a rare myeloproliferative neoplasm characterized by progressive bone marrow fibrosis and splenomegaly. Ruxolitinib is the standard-of-care first-line treatment option for MF. This review summarizes real-world effectiveness and safety of ruxolitinib in more than 4500 patients with MF from real-world settings, including expanded-access and phase 4 trials, as well as registry, postmarketing, and retrospective studies in the 10 years since regulatory approval. Consistent with results from the phase 3 COMFORT trials, real-world evidence supports the effectiveness of ruxolitinib in improving splenomegaly and MF symptoms while significantly increasing overall survival. Real-world safety data have also been aligned with results from the COMFORT trials. Transient anemia, thrombocytopenia, and infections are the most frequently observed adverse events (AEs) but rarely required ruxolitinib discontinuation. Other nonhematologic AEs are generally mild, and grade ≥ 3 events rarely occur. Importantly, real-world evidence also supports the effectiveness of ruxolitinib in patient groups that were poorly represented in clinical trials, including those with lower-risk MF, those presenting with thrombocytopenia or anemia, and those who have previously discontinued ruxolitinib treatment. Finally, cost-effectiveness analyses show ruxolitinib to be cost-effective in Europe and North America. Taken together, real-world studies reinforce the efficacy, safety, and cost-effectiveness of ruxolitinib for the treatment of patients with MF, supporting results from prospective clinical trials. Furthermore, they demonstrate the clinical benefit of ruxolitinib in patient subgroups poorly represented in clinical trials and the value of dose modifications or re-treatment after interruptions to optimize outcomes.
骨髓纤维化（MF）是一种罕见的骨髓增殖性肿瘤，其特征为进行性骨髓纤维化和脾肿大。芦可替尼是MF的标准一线治疗选择。本综述总结了芦可替尼在超过4500例来自真实世界环境的MF患者中的真实有效性和安全性，这些患者来自扩大入组试验和4期试验，以及自获批以来10年的注册登记、上市后和回顾性研究。与3期COMFORT试验的结果一致，真实世界证据支持芦可替尼在改善脾肿大和MF症状同时显著提高总生存率方面的有效性。真实世界的安全性数据也与COMFORT试验的结果一致。短暂性贫血、血小板减少和感染是最常观察到的不良事件（AE），但很少需要停用芦可替尼。其他非血液学AE通常较轻，≥3级事件很少发生。重要的是，真实世界证据还支持芦可替尼在临床试验中代表性不足的患者群体中的有效性，包括低风险MF患者、出现血小板减少或贫血的患者以及之前已停用芦可替尼治疗的患者。最后，成本效益分析表明芦可替尼在欧洲和北美具有成本效益。综上所述，真实世界研究强化了芦可替尼治疗MF患者的疗效、安全性和成本效益，支持了前瞻性临床试验的结果。此外，它们证明了芦可替尼在临床试验中代表性不足的患者亚组中的临床益处，以及剂量调整或中断后重新治疗以优化结局的价值。
