JAK 抑制剂 (JAKi) 的出现开启了骨髓纤维化 (MF) 治疗的新时代，骨髓纤维化是一种具有异质性临床表现的骨髓增殖性肿瘤。四种 JAKi 已在美国被批准用于中度或高风险 MF。 2011 年，第一个 JAK1/2 抑制剂鲁索替尼 (ruxolitinib) 获得监管部门批准，通过显着控制脾肿大和全身症状、改善患者的生活并延长生存期，改变了 MF 的面貌。 Fedratinib 是第二个获批的 JAKi，是二线治疗的首选。 Ruxolitinib 和 fedratinib 可引起骨髓抑制，推荐用于骨髓增生性 MF 患者。两种骨髓抑制性较低的 JAKi 药物 pacritinib 和 momelotinib 的批准，分别为患有严重血小板减少症和贫血的患者提供了必要的治疗选择。 Pacritinib 和 momelotinib 是有效的 ACVR1 抑制剂，可显着改善贫血。使用莫洛替尼在严重贫血患者中实现了输血独立，并证明了输血独立与延长总生存期的相关性。通过深入了解 JAKi 的关键临床试验及其治疗属性，可以做出明智的 JAKi 治疗决策，并应以主要临床表现和血细胞减少的类型/程度为指导。本文通过提供 3 个临床片段回顾了我们在 MF 患者中使用 JAKi 进行治疗的临床方法及其测序。版权所有 © 2024 美国血液学会。

The advent of JAK inhibitors (JAKi) inaugurated a novel era in the treatment of myelofibrosis (MF), a myeloproliferative neoplasm with heterogeneous clinical manifestations. Four JAKi have been approved for intermediate or high-risk MF, in the US. Regulatory approval of the first JAK1/2 inhibitor, ruxolitinib, in 2011 transformed the landscape of MF by markedly controlling splenomegaly and constitutional symptoms, improving patients' lives, and prolonging survival. Fedratinib, the second approved JAKi, is preferred in the second-line setting. Ruxolitinib and fedratinib can cause myelosuppression and are recommended for patients with myeloproliferative MF. Approval of 2 less myelosuppressive JAKi, pacritinib and momelotinib, provided essential treatment options for patients with severe thrombocytopenia and anemia, respectively. Pacritinib and momelotinib are potent ACVR1 inhibitors, resulting in significant anemia benefits. Transfusion independence was achieved with momelotinib in severely anemic patients, and association of transfusion independence with prolonged overall survival was demonstrated. Judicious treatment decisions of JAKi can be made with in-depth understanding of the pivotal clinical trials on JAKi and their therapeutic attributes and should be guided by the dominant clinical manifestations and the type/degree of cytopenia(s). This article reviews our clinical approach to treatment with JAKi and their sequencing in MF patients by presenting 3 clinical vignettes.Copyright © 2024 American Society of Hematology.