Midostaurin and gilteritinib are FLT3 inhibitors that have been recently approved for use in FLT3-mutant acute myeloid leukemia (AML). These approved drugs represent a new standard of care for patients with FLT3 mutations in both the first-line and salvage settings. The success of midostaurin used in combination with induction chemotherapy has prompted exploration of newer, more potent and targeted inhibitors (including gilteritinib) in the first-line setting in combination with chemotherapy. At the same time, the success of gilteritinib and other newer FLT3 inhibitors as monotherapy in the salvage setting has been tempered by the development of resistance because of diverse mechanisms. Investigational strategies that incorporate FLT3 inhibitors in combination with hypomethylating agents and as maintenance therapy after allogeneic stem cell transplantation have shown promise. Other novel combination strategies are also undergoing clinical investigation. In this article, we review the current landscape of approved and investigational FLT3 inhibitors in AML, including the current standard of care and investigational strategies.

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