Definition and management of ruxolitinib treatment failure in myelofibrosis.
Definition and management of ruxolitinib treatment failure in myelofibrosis.
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DOI：
10.1038/bcj.2014.84
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发表时间：
2014-12-12
影响因子：
12.8
通讯作者：
Tefferi A
中科院分区：
文献类型：
--
作者：
Pardanani A;Tefferi A
Ruxolitinib是一种Janus激酶(JAK)-1和JAK-2抑制剂，是美国批准用于治疗高和中危骨髓纤维化（MF）的首个同类药物。其他几种JAK抑制剂正在开发中，其中一些目前正在进行3期临床试验测试。目前没有一种可用的JAK抑制剂对JAK2突变体具有特异性；它们的作用机制是通过下调促炎细胞因子来减弱JAK-STAT信号，而不是选择性抑制疾病克隆。因此，虽然ruxolitinib和其他JAK抑制剂在控制脾大和缓解体质症状方面有效，但它们在逆转骨髓纤维化或诱导完全或部分缓解方面的益处似乎有限。迄今为止使用ruxolitinib的经验表明，尽管它对生活质量有有益的影响，但超过一半的患者在2-3年内停止治疗。在目前的情况下，我们根据我们的个人经验以及对已发表的文献的回顾，研究鲁索利替尼在MF患者中“治疗失败”的发生率和原因。我们还讨论了定义和分类ruxolitinib失败的挑战，并在几种临床情况的背景下，我们提供了ruxolitinib后MF患者管理的建议。
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.
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影响因子：
11.4
作者：
Barosi G;Tefferi A;Besses C;Birgegard G;Cervantes F;Finazzi G;Gisslinger H;Griesshammer M;Harrison C;Hehlmann R;Hermouet S;Kiladjian JJ;Kröger N;Mesa R;Mc Mullin MF;Pardanani A;Passamonti F;Samuelsson J;Vannucchi AM;Reiter A;Silver RT;Verstovsek S;Tognoni G;Barbui T
通讯作者：
Barbui T
影响因子：
20.3
作者：
Heine, Annkristin;Held, Stefanie Andrea Erika;Brossart, Peter
通讯作者：
Brossart, Peter
影响因子：
64.8
作者：
James, C;Ugo, V;Vainchenker, W
通讯作者：
Vainchenker, W
影响因子：
20.3
作者：
Cervantes, Francisco;Vannucchi, Alessandro M.;Gisslinger, Heinz
通讯作者：
Gisslinger, Heinz
影响因子：
1.8
作者：
Colomba C;Rubino R;Siracusa L;Lalicata F;Trizzino M;Titone L;Tolomeo M
通讯作者：
Tolomeo M