Advances in clinical studies of FLT3 inhibitors in acute myeloid leukemia

by Selleckchem | Jun 26 2023

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.

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Title: Current Status and Treatment Strategies of FLT3 Inhibitors in Acute Myeloid Leukemia: A Comprehensive Review

Abstract: Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy characterized by the presence of various genetic mutations. Patients with FLT3 mutations often exhibit a high relapse rate and poor outcomes, making the FLT3 gene an important target for AML treatment. In recent years, several FLT3 inhibitors have been developed and undergone clinical trials. This review article provides an overview of the current status of FLT3 inhibitors in clinical research for AML patients and discusses their efficacy in treating FLT3-resistant cases. Three FLT3 inhibitors, Midostaurin, Quizartinib, and Gilteritinib, have been approved for the treatment of AML patients. FLT3 inhibitors, when combined with standard chemotherapy, have shown promise in improving response rates. Additionally, FLT3 inhibitors used in follow-up maintenance treatment have demonstrated the ability to reduce disease recurrence rates and improve overall patient prognosis. However, primary drug resistance stemming from the bone marrow microenvironment, as well as secondary resistance resulting from other mutations, can limit the efficacy of FLT3 inhibitors. For patients experiencing such resistance, combination therapies involving FLT3 inhibitors and other drugs have been investigated to mitigate the development of drug resistance and enhance treatment outcomes. This review aims to provide clinicians with valuable insights into the clinical research and treatment strategies concerning FLT3 inhibitors in AML.

Keywords: Acute myeloid leukemia, AML, FLT3, FLT3 inhibitors, Midostaurin, Quizartinib, Gilteritinib, drug resistance, combination therapy, treatment strategies