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评估 ASCIMIB 用于治疗既往接受过≥2 种酪氨酸激酶抑制剂治疗的慢性髓性白血病患者。

An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors.

机构信息

Servicio de Hematología, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain.

Servicio de Hematología, Hospital Clínico Universitario, INCLIVA, University of Valencia, Valencia, Spain.

出版信息

Expert Rev Hematol. 2022 Jun;15(6):477-484. doi: 10.1080/17474086.2022.2080049. Epub 2022 May 30.

Abstract

INTRODUCTION

To date, five tyrosine kinase inhibitors (TKIs) are available for treating chronic myeloid leukemia (CML) patients in clinical practice. Despite this, a significant proportion of patients will ultimately develop failure to approved TKIs due to intolerance or resistance. Consequently, new treatment approaches are still required in this unmet clinical need. Asciminib, a first-in-class BCR::ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to prior TKI treatment.

AREAS COVERED

This review will cover the mechanism of action, pharmacokinetic profile, and clinical data of asciminib based on available information from laboratory studies, clinical trials, and real-world evidence.

EXPERT OPINION

Recent approval of asciminib will require positioning of this drug in the treatment algorithm of CML patients failing initial TKI therapy. Available data support the lack of cross-intolerance of asciminib with other TKIs and its favorable cardiovascular toxicity profile. In addition, asciminib has demonstrated considerable efficacy in CML patients who have failed at least two TKIs, although preliminary data suggest that this efficacy may be lower in those previously exposed to ponatinib. The introduction of asciminib in clinical practice may represent an important step forward in the management of CML.

摘要

简介

迄今为止,已有五种酪氨酸激酶抑制剂(TKI)可用于临床治疗慢性髓性白血病(CML)患者。尽管如此,由于不耐受或耐药,仍有相当一部分患者最终会对已批准的 TKI 治疗失败。因此,在这一未满足的临床需求中,仍需要新的治疗方法。Asciminib 是一种首创的靶向 ABL 豆蔻酰口袋(STAMP)的 BCR::ABL1 抑制剂,有可能克服对先前 TKI 治疗的耐药性/不耐受。

涵盖领域

本综述将根据实验室研究、临床试验和真实世界证据中的可用信息,涵盖 asciminib 的作用机制、药代动力学特征和临床数据。

专家意见

asciminib 的最近批准将要求将该药物定位在初始 TKI 治疗失败的 CML 患者的治疗算法中。现有数据支持 asciminib 与其他 TKI 之间缺乏交叉不耐受性及其有利的心血管毒性特征。此外,asciminib 在至少两种 TKI 治疗失败的 CML 患者中显示出相当大的疗效,尽管初步数据表明,对于先前暴露于 ponatinib 的患者,这种疗效可能较低。asciminib 在临床实践中的引入可能代表着 CML 管理方面的重要进步。

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