Leukemia research · 2024
Phase 1 study of azacitidine in combination with quizartinib in patients with FLT3 or CBL mutated MDS and MDS/MPN.
СтатьяКлиническое исследование I фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Montalban-Bravo Guillermo, Jabbour Elias, Chien Kelly, Hammond Danielle, Short Nicholas, Ravandi Farhad, Konopleva Marina, Borthakur Gautam, Daver Naval, Kanagal-Shammana Rashmi, Loghavi Sanam, Qiao Wei, Huang Xuelin, Schneider Heather, Meyer Meghan, Kantarjian Hagop, Garcia-Manero Guillermo
Аннотация
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.