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  • Title: Midostaurin for the treatment of adult patients with newly diagnosed acute myeloid leukemia that is FLT3 mutation-positive.
    Author: Garcia JS, Percival ME.
    Journal: Drugs Today (Barc); 2017 Oct; 53(10):531-543. PubMed ID: 29286055.
    Abstract:
    Midostaurin is a multitargeted tyrosine kinase inhibitor (TKI) that potently inhibits activated fms-related tyrosine kinase 3 (FLT3) in the nanomolar range and other kinases including platelet-derived growth factor receptors α (PDGFR- α) and β (PDGFR- β), cyclin-dependent kinase, proto-oncogene tyrosine-protein kinase Src, tyrosine-protein kinase Fgr, spleen tyrosine kinase (Syk), KIT proto-oncogene receptor tyrosine kinase and the major vascular endothelial growth factor receptor (VEGFR). Activating mutations in FLT3, which is one of the more common acute myeloid leukemia (AML) mutations, particularly those that result in an FLT3-ITD (internal tandem duplication) mutation, confer poor prognosis and represent a therapeutic target. Small molecule TKIs that vary in potency and selectivity for FLT3 are under investigation. Here, we provide a comprehensive review of the preclinical and clinical activity of midostaurin, a recently approved drug indicated to be used in combination with cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy for the treatment of AML featuring an FLT3 mutation.
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