Clinical use of FLT3 inhibitors in acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease. Mutation with internal tandem duplication of fms-like tyrosine kinase-3 (FLT3-ITD) is one of the two most common driver mutations and the presence of FLT3-ITD delivers poor prognosis. A number of ongoing clinical efforts are focused on FLT3 inhibitor use to improve the outcomes of this otherwise difficult leukemia. Midostaurin has been shown to improve outcomes in FLT3-mutated AML in the frontline setting. Several FLT3 inhibitors, especially second-generation agents, have shown clinically meaningful activity in relapsed or refractory AML and in patients not amenable to intensive therapy. In this article, we briefly review the biology of FLT3 in the physiological state and its role in leukemogenesis. We present a detailed review of current clinical evidence of FLT3 inhibitors and their use in the induction, treatment of relapsed or refractory disease, and maintenance setting.