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Minerva Med ; 111(5): 443-454, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32955824

ABSTRACT

Mutation within the FMS-like tyrosine kinase 3 (FLT3) gene are one of the most frequent genetic alterations in acute myeloid leukemia. A high mutation fraction of FLT3-ITD molecules on the surface of leukemia cells is associated with short remissions and overall adverse outcomes in AML. In this article we summarize the clinical trial data of midostaurin - one of the FLT3 inhibitors. We review its use in various combinations both in relapsed/refractory acute myeloid leukemia as well as in the newly diagnosed patients and recollect the evidence of its use as maintenance therapy post allogenic stem cell transplantation. We enumerate the practical issues faced in the use of midostaurin like antifungal prophylaxis, dosage of concomitant chemotherapy agents as well as available data on sequencing of the FLT3 inhibitors. Lastly, we provide our perspective of the future directions for FLT3 inhibition especially midostaurin, the underlying resistance mechanisms and the need for standardization of the FLT3 tests.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Protein Kinase Inhibitors/therapeutic use , Staurosporine/analogs & derivatives , fms-Like Tyrosine Kinase 3/genetics , Aniline Compounds/therapeutic use , Anthracyclines/therapeutic use , Antifungal Agents/therapeutic use , Antineoplastic Agents/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials as Topic , Cytarabine/therapeutic use , Cytochrome P-450 CYP3A Inhibitors/pharmacology , Drug Interactions , Echinocandins/therapeutic use , Forecasting , Hematopoietic Stem Cell Transplantation , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Maintenance Chemotherapy , Mutation , Mycoses/prevention & control , Protein Kinase Inhibitors/metabolism , Pyrazines/therapeutic use , Randomized Controlled Trials as Topic , Recurrence , Staurosporine/metabolism , Staurosporine/therapeutic use , Triazoles/therapeutic use , fms-Like Tyrosine Kinase 3/antagonists & inhibitors
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