The potential of triplet combination therapies for patients with FLT3-ITD -mutated acute myeloid leukemia.

IF 2.3 4区医学 Q2 HEMATOLOGY Expert Review of Hematology Pub Date : 2024-06-01 Epub Date: 2024-05-20 DOI:10.1080/17474086.2024.2356258

Antonella Bruzzese, Ernesto Vigna, Enrica Antonia Martino, Caterina Labanca, Francesco Mendicino, Eugenio Lucia, Virginia Olivito, Gaia Stanzione, Annamaria Zimbo, Elisabetta Lugli, Antonino Neri, Fortunato Morabito, Massimo Gentile

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Abstract

Introduction: Acute myeloid leukemia (AML) encompasses a heterogeneous group of aggressive myeloid malignancies, where FMS-like tyrosine kinase 3 (FLT3) mutations are prevalent, accounting for approximately 25-30% of adult patients. The presence of this mutation is related to a dismal prognosis and high relapse rates. In the lasts years many FLT3 inhibitors have been developed.

Areas covered: This review provides a comprehensive overview of FLT3^mut AML, summarizing the state of art of current treatment and available data about combination strategies including an FLT3 inhibitor.

Expert opinion: In addition, the review discusses the emergence of drug resistance and the need for a nuanced approaches in treating patients who are ineligible for or resistant to intensive chemotherapy. Specifically, it explores the historical context of FLT3 inhibitors (FLT3Is) and their impact on treatment outcomes, emphasizing the pivotal role of midostaurin, as well as gilteritinib and quizartinib, and providing detailed insights into ongoing trials exploring the safety and efficacy of novel triplet combinations involving FLT3Is in different AML settings.

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三联疗法治疗 FLT3-ITD 突变急性髓性白血病患者的潜力。

简介急性髓性白血病（AML）是一类异质性侵袭性髓性恶性肿瘤，其中FMS样酪氨酸激酶3（FLT3）突变最为常见，约占成年患者的25%-30%。这种突变与预后不良和高复发率有关。近年来，许多 FLT3 抑制剂相继问世：本综述全面概述了FLT3突变型急性髓细胞白血病，总结了当前治疗的最新进展以及包括FLT3抑制剂在内的联合治疗策略的可用数据：此外，该综述还讨论了耐药性的出现，以及在治疗不符合强化化疗条件或对强化化疗产生耐药性的患者时采取细致入微的方法的必要性。具体而言，该综述探讨了FLT3抑制剂（FLT3Is）的历史背景及其对治疗结果的影响，强调了米哚妥林以及吉特替尼和奎沙替尼的关键作用，并详细介绍了正在进行的试验，这些试验探索了FLT3Is在不同急性髓细胞性白血病中新型三联疗法的安全性和有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Expert Review of Hematology HEMATOLOGY-

CiteScore

4.70

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.