文章：

鲁索利替尼治疗骨髓纤维化失败的定义和处理

Definition and management of ruxolitinib treatment failure in myelofibrosis

原文发布日期：2014-12-12

DOI: 10.1038/bcj.2014.84

类型: Original Article

开放获取: 是

英文摘要：

Ruxolitinib, a Janus kinase (JAK)-1 and JAK-2 inhibitor, is the first-in-class drug to be licensed in the United States for the treatment of high- and intermediate-risk myelofibrosis (MF). Several other JAK inhibitors are in development with some currently undergoing phase-3 clinical trial testing. None of the currently available JAK inhibitors are specific to mutant JAK2; their mechanism of action involves attenuation of JAK-STAT signaling with downregulation of proinflammatory cytokines, rather than selective suppression of the disease clone. Accordingly, while ruxolitinib and other JAK inhibitors are effective in controlling splenomegaly and alleviating constitutional symptoms, their benefit in terms of reversing bone marrow fibrosis or inducing complete or partial remissions appears to be limited. The experience to date with ruxolitinib shows that despite its salutary effects on quality of life, over half of the patients discontinue treatment within 2–3 years. In the current perspective, we examine the incidence and causes of ruxolitinib ‘treatment failure’ in MF patients based on our personal experience as well as a review of the published literature. We also discuss the challenges in defining and classifying ruxolitinib failure, and within the context of several clinical scenarios, we provide recommendations for the post-ruxolitinib management of MF patients.

摘要翻译： 

鲁索替尼是一种Janus激酶（JAK）-1和JAK-2抑制剂，是美国首个获批用于治疗中高危骨髓纤维化（MF）的同类首创药物。目前还有数种其他JAK抑制剂正在研发中，其中部分已进入三期临床试验阶段。现有JAK抑制剂均非针对突变型JAK2的特异性药物，其作用机制是通过下调促炎细胞因子来减弱JAK-STAT信号传导，而非选择性抑制病变克隆。因此，虽然鲁索替尼和其他JAK抑制剂能有效控制脾肿大并改善全身症状，但在逆转骨髓纤维化或诱导完全/部分缓解方面的获益似乎有限。现有使用经验表明，尽管鲁索替尼能显著改善生活质量，但超过半数患者会在2-3年内终止治疗。本文基于我们的临床实践和文献综述，探讨骨髓纤维化患者鲁索替尼"治疗失败"的发生率及原因。我们同时讨论了定义和分类鲁索替尼治疗失败面临的挑战，并结合多种临床情境为鲁索替尼治疗后骨髓纤维化患者的管理提出建议。

原文链接：

Definition and management of ruxolitinib treatment failure in myelofibrosis