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评估 fedratinib 用于新诊断和既往治疗的成人骨髓纤维化患者。

An evaluation of fedratinib for adult patients with newly diagnosed and previously treated myelofibrosis.

机构信息

Department of Hematology, Gustave Roussy Cancer Campus, Villejuif, France.

Departement d'Innovation Therapeutique Et d'Essais Precoces (DITEP), Gustave Roussy Cancer Campus, Villejuif, France.

出版信息

Expert Rev Hematol. 2023 Apr;16(4):227-236. doi: 10.1080/17474086.2023.2192473. Epub 2023 Mar 21.

Abstract

INTRODUCTION

Myelofibrosis (MF) is a life-shortening myeloproliferative neoplasm that has multiple features such as clonal proliferation, fibrosis and splenomegaly. Until recently, ruxolitinib, a Janus Kinase (JAK) 1/2 inhibitor was the only targeted therapy approved for transplant-ineligible patients with MF and who require treatment for symptoms and/or splenomegaly. However, the discontinuation rate with ruxolitinib at 3 to 5 years is high and mostly due to loss of response or toxicity, and these patients had no subsequent treatment.

AREAS COVERED

Fedratinib, a selective JAK2 inhibitor, was approved by the Food and Drug Administration (FDA) in August 2019 for the treatment of intermediate-2 or high-risk primary or secondary MF, regardless of prior JAK inhibitor treatment for the management of symptoms and splenomegaly. We discuss herein the development of fedratinib and its pharmacology and pharmacokinetics as well as the clinical development and the future directions. We used PubMed for the search of articles related to fedratinib and myelofibrosis.

EXPERT OPINION

Fedratinib provided a second-line treatment for patients with MF who failed or discontinued ruxolitinib. New combinations of JAK inhibitors with other targeted therapies are a must in order to improve the management of MF.

摘要

简介

骨髓纤维化(MF)是一种缩短生命的骨髓增殖性肿瘤,具有克隆性增殖、纤维化和脾肿大等多种特征。直到最近,鲁索替尼(一种 Janus 激酶(JAK)1/2 抑制剂)才是唯一被批准用于不适合移植的 MF 患者和需要治疗症状和/或脾肿大的患者的靶向治疗药物。然而,鲁索替尼在 3 至 5 年内的停药率很高,主要是由于失去反应或毒性,这些患者没有后续治疗。

涵盖领域

Fedratinib,一种选择性 JAK2 抑制剂,于 2019 年 8 月被美国食品和药物管理局(FDA)批准用于治疗中 2 或高风险原发性或继发性 MF,无论先前是否使用 JAK 抑制剂治疗症状和脾肿大。我们在此讨论 fedratinib 的开发及其药理学和药代动力学,以及临床开发和未来方向。我们使用 PubMed 搜索了与 fedratinib 和骨髓纤维化相关的文章。

专家意见

Fedratinib 为鲁索替尼治疗失败或停药的 MF 患者提供了二线治疗。为了改善 MF 的治疗,必须将 JAK 抑制剂与其他靶向疗法联合使用。

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