Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. AML patients with FLT3 mutations tend to have a high relapse rate and poor outcome, so FLT3 gene 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 FLT3 inhibitors. 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, FLT3 inhibitors 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.