Quizartinib for Newly Diagnosed FLT3 -ITD–Negative Acute Myeloid Leukemia: The Randomized, Double-Blind, Placebo-Controlled, Phase 2 QUIWI Study

BACKGROUND Quizartinib, an oral, selective, second-generation, type-II FMS-like tyrosine kinase 3 (FLT3) inhibitor with high binding affinity to internal tandem duplication (ITD) and wild-type FLT3, has shown early clinical activity as monotherapy in patients with relapsed/refractory FLT3 -ITD–negative acute myeloid leukemia (AML). The phase 3 QuANTUM-First trial showed that quizartinib significantly prolonged survival vs placebo when added to standard chemotherapy, followed by single-agent maintenance, in patients with newly diagnosed (ND) FLT3- ITD–positive AML. We investigated the safety and efficacy of quizartinib in patients with ND FLT3 -ITD–negative AML. METHODS The phase 2, randomized, double-blind, placebo-controlled QUIWI trial enrolled patients aged 18–70 years with ND FLT3 -ITD–negative (mutant-to-wild-type allelic ratio <0.03) AML. Patients were randomized 2:1 to receive standard induction and consolidation chemotherapy combined with either quizartinib 60 mg daily or placebo, followed by single-agent maintenance with quizartinib or placebo. The primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival (OS) and safety. RESULTS Overall, 273 patients were randomized to quizartinib (n=180) or placebo (n=93). At data cutoff, median EFS was 20.4 months and 9.9 months in the quizartinib and placebo arms, respectively ( P =0.046). Median OS was not reached and 29.3 months in the quizartinib and placebo arms, respectively ( P =0.012); three-year OS rates were 60.8% and 45.7%. The most frequently reported adverse events (any grade) were fever, rash, diarrhea, and mucositis. CONCLUSIONS The addition of quizartinib to standard chemotherapy was associated with significantly longer EFS and OS than placebo in patients with ND FLT3 -ITD–negative AML. ClinicalTrials.gov NCT04107727 .