Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Expert Rev Hematol. 2013 Oct;6(5):511-23. doi: 10.1586/17474086.2013.827413. Epub 2013 Oct 2.
Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients also experience debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi, Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA for the treatment of intermediate- or high-risk MF, and more recently in Europe and Canada for the treatment of MF-related splenomegaly or symptoms. These approvals were based on data from two randomized Phase III studies: COMFORT-I randomized against placebo, and COMFORT-II randomized against best available therapy. In these studies, ruxolitinib rapidly improved multiple disease manifestations of MF, reducing splenomegaly and improving quality of life of patients and potentially prolonging survival. However, as with other chemotherapies, ruxolitinib therapy is associated with some adverse events, such as anemia and thrombocytopenia. The aims of this article are to provide a brief overview of ruxolitinib therapy, to discuss some common adverse events associated with ruxolitinib therapy and to provide clinical management recommendations to maximize patients' benefit from ruxolitinib.
骨髓纤维化(MF)的特征为骨髓纤维化、进行性贫血和髓外造血,主要表现为脾肿大。患者还会出现使人虚弱的全身症状,包括脾肿大、盗汗和疲劳的后遗症。罗昔替尼(INC424、INCB18424、Jakafi、Jakavi)是一种 JAK1 和 JAK2 抑制剂,于 2011 年 11 月被美国 FDA 批准用于治疗中高危 MF,最近在欧洲和加拿大也被批准用于治疗 MF 相关的脾肿大或症状。这些批准是基于两项随机 III 期研究的数据:COMFORT-I 与安慰剂对照,COMFORT-II 与最佳可用疗法对照。在这些研究中,罗昔替尼迅速改善了 MF 的多种疾病表现,减少了脾肿大,改善了患者的生活质量,并可能延长了生存时间。然而,与其他化疗药物一样,罗昔替尼治疗也与一些不良反应相关,如贫血和血小板减少症。本文旨在简要概述罗昔替尼治疗,并讨论一些与罗昔替尼治疗相关的常见不良反应,为最大限度地提高患者从罗昔替尼治疗中获益提供临床管理建议。