Fedratinib治疗骨髓纤维化的研究新进展

State of art:fedratinib for treatment of patients with myelofibrosis

骨髓纤维化(MF)属于Ph呈阴性骨髓增殖性肿瘤(MPN),包括原发性骨髓纤维化(PMF)、真性红细胞增多症后(post-PV)MF和特发性血小板增多症后(post-ET)MF。JAK2V617F基因突变是MF患者的主要致病基因突变。针对Janus激酶(JAK)/信号转导和转录激活因子(STAT)信号通路的第2代抑制剂fedratinib于2019年8月获美国食品与药品监督管理局(FDA)批准上市,用于治疗国际预后积分系统(IPSS)中危-2及高危MF成年患者。该药既可用于一线治疗,也可用于第1代JAK/STAT信号通路抑制剂芦可替尼耐药或者不耐受患者的二线治疗。笔者拟就fedratinib的药理学特性及其治疗MF的作用机制、临床疗效、治疗相关不良反应和耐药机制的研究最新进展进行阐述。

Myelofibrosis(MF)is one of Ph negative myeloproliferative neoplasms(MPN).It could be present as primary myelofibrosis(PMF),post-polycythemia vera(post-PV)MF and post-essential thrombocythemia(post-ET)MF.JAK2V617F mutation is the common driver gene mutation of MF.Fedratinib is a secondary generation inhibitor of Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway which have received approval by United States Food and Drug Administration(FDA)for the treatment of adult patients with International Prognostic Scoring System(IPSS)intermediate-2 or high-risk MF in August 2019,both as a first-line therapy or second-line therapy following first generation JAK/STAT signaling pathway inhibitor ruxolitinib intolerance or resistance.This article summarizes research progress of the pharmacological properties,mechanism of action,clinical efficacy,adverse reactions and drug resistance mechanism of fedratinib in the treatment of MF.