Servicio de Farmacia, Área del Medicamento. Hospital Universitari i Politècnic La Fe. Av. Fernando Abril Martorell, Valencia- Spain.
Instituto de Investigación Sanitaria La Fe (IISLAFE). Av. Fernando Abril Martorell, Valencia-Spain.
Expert Opin Emerg Drugs. 2022 Mar;27(1):1-18. doi: 10.1080/14728214.2021.2009800. Epub 2022 Jan 25.
The FMS-like tyrosine kinase 3 (FLT3) gene is mutated in one-third of patients with Acute Myeloid Leukemia (AML). Midostaurin, quizartinib, and gilteritinib have been approved in the last years for the treatment of AML, and more Tyrosine Kinase Inhibitors (TKIs) targeting FLT3 are being developed such as crenolanib.
In this systematic review, we will analyze the available clinical data on FLT3 inhibitors in development and describe the potential role that these FLT3-TKIs may play in the future management of FLT3-mutated (FLT3mut) AML.
Although several aspects may challenge the use of FLT3 inhibitors in AML (resistance mechanisms, on- and off-target toxicities or drug-drug interactions), these drugs are generally well tolerated, particularly if we compare their safety profile with classical chemotherapy agents or even with newer immunotherapies, thus enabling their use in fit and unfit AML patients, alone or combined. As AML is a polyclonal disease and FLT3 mutations are a late leukemogenic event, combinations of these FLT3 inhibitors with other antileukemic agents (like venetoclax or hypomethylating agents) seem a necessary research pathway.
FMS 样酪氨酸激酶 3（FLT3）基因在三分之一的急性髓系白血病（AML）患者中发生突变。近年来，米哚妥林、quizartinib 和 gilteritinib 已被批准用于 AML 的治疗，更多针对 FLT3 的酪氨酸激酶抑制剂（TKI）正在开发中，如 crenolanib。
在本次系统评价中，我们将分析正在开发的 FLT3 抑制剂的现有临床数据，并描述这些 FLT3-TKI 在未来治疗 FLT3 突变（FLT3mut）AML 中可能发挥的作用。
尽管有几个方面可能会影响 AML 中 FLT3 抑制剂的使用（耐药机制、脱靶和靶外毒性或药物相互作用），但这些药物通常耐受性良好，尤其是与传统化疗药物甚至新型免疫疗法相比，因此可用于适合和不适合的 AML 患者，单独使用或联合使用。由于 AML 是一种多克隆疾病，FLT3 突变是晚期白血病发生的事件，因此将这些 FLT3 抑制剂与其他抗白血病药物（如 venetoclax 或低甲基化剂）联合使用似乎是必要的研究途径。
