Quizartinib (FLT3 inhibitor) + decitabine/venetoclax drives 89% CR/CRi and 36.5-mo OS in older frontline FLT3-ITD AML

Quizartinib (QUIZ) is an oral, potent FLT3 inhibitor combined with decitabine (DNA hypomethylating agent) and venetoclax (BCL-2 inhibitor) in a Phase I/II study (NCT03661307) enrolling newly diagnosed FLT3-ITD AML unfit for intensive chemotherapy (n=42; median age 70) and R/R FLT3-ITD AML (n=46); QUIZ 26.5mg daily was the RP2D. Frontline efficacy was CR 72% (29/40), CRi 17% (7/40), MLFS 2% (1/40) with EOC1 MRD-negativity 58% by MFC (19/32) and 27% FLT3-ITD-negativity by high-sensitivity NGS (5/18); median RFS 24.7mo and median OS 36.5mo (36% bridged to allo-SCT, with OS not reached vs 36.6mo without SCT; p=0.65). These outcomes look substantially above historical HMA+VEN benchmarks in unfit newly diagnosed AML (e.g., VIALE-A azacitidine+VEN median OS 14.7mo; CR 37%), while safety remained dominated by expected myelosuppression/infection complications—grade ≥3 febrile neutropenia 37%, pneumonia 33%, infections 17%, sepsis 9% plus notable non-hematologic signals (ALT increase 10%, fractures 10%, pleural effusion 7%).