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Editorials
supports an eventual trial of a BET inhibitor in combina- tion with a FLT3 inhibitor in patients with mutant FLT3 AML.8 The idea is to injure the malignant cells with a FLT3 inhibitor and deprive them of their ‘comfort zone’ with the BET inhibitor. With an increase in potentially useful molecules in AML, the solid pre-clinical studies such as those described by Lee et al.8 are needed to choose the most potentially useful combinations for clinical use.
Disclosures
RMS has sat on ad hoc boards and has had a consultancy role for Hoffman-LaRoche, Pfizer, Otsuka, Novartis, Jazz, Celgene, Astellas, Arog, Amgen, Agios, Actinum, Abbvie, Takeda, Macrogneics, Janssen, Gemoab, Daichii-Sanko, Biolinerx, Trovagene, Stemline, AStraZeneca, Elevate Bio, BerGenBio, Foghorn, Innate Pharma. GSK, Syndax, and Syros. He has been Principal Investigator for clinical research of his institution with Agios, Abbvie, Syndax, and Lilly. He has sat on the Data Safety and Monitoring Board for Celgene, Takeda, Argenix, and Syntax Clinical.
References
1. Dohner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
2. Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 muta- tions in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299-312.
3.Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-464.
4. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med. 2019;381(18):1728-1740.
5. McMahon CM, Ferng T, Canaani J, et al. Clonal selection with RAS pathway activation mediates secondary clinical resistance to selec- tive FLT3 inhibition in acute myeloid leukemia. Cancer Discov. 2019;9(8):1050-1063.
6. Shi J, Vakoc CR. The mechanisms behind the therapeutic activity of BET bromodomain inhibition. Mol Cell. 2014;54(5):728-736.
7. Yang X, Sexauer A, Levis M. Bone marrow stroma-mediated resist- ance to FLT3 inhibitors in FLT3-ITD AML is mediated by persistent activation of extracellular regulated kinase. Br J Haematol. 2014;164(1):61-72.
8. Lee L, Hizukuri Y, Severson P, et al. A novel combination regimen of BET and FLT3 inhibition for FLT3-ITD acute myeloid leukemia. Haematologica. 2021;106(4):1022-1033.
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