The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Leuk Lymphoma. 2023 Jun;64(6):1063-1081. doi: 10.1080/10428194.2023.2196593. Epub 2023 Apr 20.
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, abnormal cytokine expression, cytopenias, and progressive bone marrow fibrosis. The disease often manifests with burdensome symptoms and is associated with reduced survival. Ruxolitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor, was the first agent approved for MF. As a first-in-class targeted treatment, ruxolitinib approval transformed the MF treatment approach and remains standard of care. In addition, targeted inhibition of JAK1/JAK2 signaling, a key molecular pathway underlying MF pathogenesis, and the large volume of literature evaluating ruxolitinib, have led to a better understanding of the disease and improved management in general. Here we review ruxolitinib efficacy in patients with MF in the 10 years following approval, including demonstration of clinical benefit in the phase 3 COMFORT-I/II trials, real-world evidence, translational studies, and expanded access data. Lastly, future directions for MF treatment are discussed, including ruxolitinib-based combination therapies.
骨髓纤维化（MF）是一种慢性骨髓增生性肿瘤，其特征为脾肿大、异常细胞因子表达、细胞减少和进行性骨髓纤维化。该疾病常表现为沉重的症状，并与生存时间减少相关。芦可替尼，一种口服 Janus 激酶（JAK）1 和 JAK2 抑制剂，是第一种获批用于 MF 的药物。作为首个获批的靶向治疗药物，芦可替尼的批准改变了 MF 的治疗方法，并成为了标准治疗方法。此外，对 MF 发病机制中关键的分子通路 JAK1/JAK2 信号的靶向抑制作用，以及大量评估芦可替尼的文献，使得我们对该疾病有了更好的理解，并总体上改善了疾病的管理。在此，我们回顾了芦可替尼在获批后的 10 年中在 MF 患者中的疗效，包括在 3 期 COMFORT-I/II 试验中显示出的临床获益、真实世界证据、转化研究和扩展使用数据。最后，讨论了 MF 治疗的未来方向，包括基于芦可替尼的联合治疗。
