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Minerva Medica 2020 Sep 21

DOI: 10.23736/S0026-4806.20.07014-7

Copyright © 2020 EDIZIONI MINERVA MEDICA

lingua: Inglese

Midostaurin in acute myeloid leukemia: review of current evidence and practical considerations in routine clinical use

Nurul A. ABDUL-HAMIL 1 , Gee C. WONG 1, 2, Chandramouli NAGARAJAN 1, 2, Giovanni MARTINELLI 3, Claudio CERCHIONE 3

1 Department of Haematology, Singapore General Hospital, Singapore; 2 SingHealth Duke-NUS Blood Cancer Center, Singapore; 3 Hematology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Forlì-Cesena, Italy


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Mutation within the fms-like tyrosine kinase 3 (FLT3) gene are one of the most frequent genetic alterations in Acute Myeloid Leukaemia. A high mutation fraction of FLT3-ITD molecules on the surface of leukaemia cells is associated with short remissions and overall adverse outcomes in AML. In this review 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 Leukaemia 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 standardisation of the FLT3 tests.


KEY WORDS: Acute myeloid leukemia; FLT3; FLT3 inhibitors; Midostaurin

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