Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Division of Hematology, Azienda Policlinico-S. Marco, University of Catania, Catania, Italy.
Expert Rev Hematol. 2024 Jun;17(6):241-253. doi: 10.1080/17474086.2024.2356258. Epub 2024 May 20.
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.
This review provides a comprehensive overview of FLT3 AML, summarizing the state of art of current treatment and available data about combination strategies including an FLT3 inhibitor.
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.
急性髓系白血病(AML)是一组异质性的侵袭性髓系恶性肿瘤,其中 FMS 样酪氨酸激酶 3(FLT3)突变较为常见,约占成年患者的 25-30%。该突变的存在与预后不良和高复发率相关。近年来,已经开发出许多 FLT3 抑制剂。
本综述全面概述了 FLT3 AML,总结了当前治疗的最新进展以及关于联合策略(包括 FLT3 抑制剂)的可用数据。
此外,该综述还讨论了耐药性的出现以及需要对不适合或对强化化疗耐药的患者采用细致方法治疗的必要性。具体而言,它探讨了 FLT3 抑制剂(FLT3Is)的历史背景及其对治疗结果的影响,强调了 midostaurin 的关键作用,以及 gilteritinib 和 quizartinib,并详细介绍了正在进行的试验,这些试验探讨了不同 AML 环境中包含 FLT3Is 的新型三联组合的安全性和疗效。