FLT3抑制剂治疗急性髓系白血病患者研究进展

Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia

急性髓系白血病(AML)是一种高度异质性的恶性血液肿瘤,其中伴FLT3基因突变患者复发率较高、预后较差,因此FLT3成为AML治疗的重要靶点。近年来,先后有第一代、第二代共8个FLT3抑制剂注册临床试验,其中可用于AML患者治疗的有米哚妥林、吉瑞替尼和奎扎替尼三种药物。FLT3抑制剂通过与标准化疗药物联用进一步提高疾病缓解率,在后续的维持治疗中,FLT3抑制剂同样可以降低患者的疾病复发率,改善患者整体预后。部分患者可出现因骨髓微环境导致的原发性耐药或用药后并发其他突变所致的继发性耐药。FLT3抑制剂与其他化疗药物联用可以减少耐药的发生。本文对常见FLT3抑制剂治疗AML患者的研究进展进行综述,以期为临床提供参考。

Acute myeloid leukemia(AML)is a highly heterogeneous hematological malignancy.AML patients withFLT3mutations tend to have a high relapse rate and poor outcome,soFLT3gene has become an important target for AML treatment,and a series of FLT3 inhibitors have been developed.According to the characteristics of FLT3 inhibitors,they can be divided into first-generation FLT3 inhibitors and second-generation FLT3inhibitors.So far,totally eight FLT3 inhibitors have been undergone clinical trials and only three were approved for the treatment of AML patients,including Midostourin,Quizartinib and Gilteritinib.FLT3 inhibitors can improve the response rate of patients by combining with standard chemotherapy;in the follow-up maintenance treatment,FLT3inhibitors can also reduce the disease recurrence rate and improve the overall prognosis of patients.However,the primary drug resistance caused by the bone marrow microenvironment,as well as secondary resistance caused by other mutations may result in poor efficacy of FLT3 inhibitors.For such patients,the combination of FLT3 inhibitor with other drugs may reduce the occurrence of drug resistance and improve the subsequent efficacy of patients.This article reviews the current status of FLT3 inhibitors in clinical research of AML patients and the treatment of FLT3-resistant patients to provide reference for clinicians.