Phase 1 study of azacitidine in combination with quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN.

Autor: Montalban-Bravo G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA. Electronic address: GMontalban1@mdanderson.org., Jabbour E; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Chien K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Hammond D; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Short N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Konopleva M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Borthakur G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Daver N; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Kanagal-Shammana R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, USA., Loghavi S; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, USA., Qiao W; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, USA., Huang X; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, USA., Schneider H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Meyer M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Kantarjian H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA., Garcia-Manero G; Department of Leukemia, The University of Texas MD Anderson Cancer Center, USA.
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2024 Jul; Vol. 142, pp. 107518. Date of Electronic Publication: 2024 May 11.
DOI: 10.1016/j.leukres.2024.107518
Abstrakt: We conducted a phase 1 study evaluating 3 dose levels of quizartinib (30 mg, 40 mg or 60 mg) in combination with azacitidine for HMA-naïve or relapsed/refractory MDS or MDS/MPN with FLT3 or CBL mutations. Overall, 12 patients (HMA naïve: n=9, HMA failure: n=3) were enrolled; 7 (58 %) patients had FLT3 mutations and 5 (42 %) had CBL mutations. The maximum tolerated dose was not reached. Most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (n=5, 42 %), anemia (n=4, 33 %), lung infection (n=2, 17 %), skin infection (n=2, 17 %), hyponatremia (n=2, 17 %) and sepsis (n=2, 17 %). The overall response rate was 83 % with median relapse-free and overall survivals of 15.1 months (95 % CI 0.0-38.4 months) and 17.5 months (95 % CI NC-NC), respectively. FLT3 mutation clearance was observed in 57 % (n=4) patients. These data suggest quizartinib is safe and shows encouraging activity in FLT3-mutated MDS and MDS/MPN. This study is registered at Clinicaltrials.gov as NCT04493138.
Competing Interests: Declaration of Competing Interest GMB declares grant/research support from Takeda, Rigel and IFM Therapeutics. M.K. declares consulting and honoraria from AbbVie, Genentech, F. Hoffman La-Roche, Stemline Therapeutics, Amgen, Forty-Seven, and Kisoji; research funding and/or clinical trial support from AbbVie, Genentech, F. Hoffman La-Roche, Eli Lilly, Cellectis, Calithera, Ablynx, Stemline Therapeutics, Agios, Ascentage, and Astra Zeneca; and stock options/royalties from Reata Pharmaceutical. H.K. declares research support from AbbVie, Agios, Amgen, Ariad, Astex, BMS, Cyclacel, Daiichi-Sankyo, Immunogen, Jazz Pharma, Novartis, and Pfizer, honoraria from AbbVie, Actinium, Agios, Amgen, Immunogen, Orsinex, Pfizer, and Takeda, and an advisory role with Actinium. G.G-M. declares support from and an advisory role with Celgene Corporation, Astex, and Amphivena, and grant/research support 15 from Helsinn, Novartis, AbbVie, Onconova, H3 Biomedicine, and Merck. S.L grant/research support from Amgen and Astellas and consulting and honoraria from Guidepoint, Qual World, Gerson Lehman Group, Caris, Blueprint Medicines Corporation, Daiichi Sankyo, Recordati, Abbvie, and Arima and owns Abbvie stocks. The rest of authors declare no competing financial interests.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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