• Marlise R Luskin and Daniel J DeAngelo.
• a Department of Medical Oncology , Dana-Farber Cancer Institute , Boston , MA , USA.
• Expert Rev Hematol. 2017 Dec 1; 10 (12): 1033-1045.

IntroductionAcute myeloid leukemia (AML) is an aggressive hematologic malignancy with inadequate treatment options. Approximately one-third of cases have a FLT3-ITD or FLT3-TKD mutation which leads to constitutive tyrosine kinase activation which contributes to leukemogenesis. The FLT3-ITD mutation is associated with a particularly poor prognosis. Midostaurin is a multi-kinase inhibitor active against the FLT3 receptor. Midostaurin was approved by the US FDA in April 2017 for treatment of newly diagnosed FLT3-mutant AML in combination with chemotherapy. Areas covered: Standard treatment of FLT3-mutant AML and outcomes. Early clinical development of midostaurin including pharmacokinetics and metabolism. The development of midostaurin in FLT3-mutant AML is then outlined including review of the phase I, II, and III trials of midostaurin as a single agent and in combination with chemotherapy. Expert commentary: The approval of midostaurin represents the first new therapy for AML in several decades. It is also the first targeted therapy approved for AML. Future studies will focus on defining mechanisms of resistance to midostaurin as well as establishing the role of midostaurin in combination with hypomethylating agents and as maintenance therapy. Second generation, more potent and selective FLT3 inhibitors are also in development; these agents need to be compared to midostaurin.

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