Impact of hematopoietic cell transplantation and quizartinib in patients with newly diagnosed FLT3-internal tandem duplication-negative acute myeloid leukemia: results from the QUIWI study.

QUIWI (NCT04107727) was a phase II, randomized, double-blind, placebo-controlled trial evaluating quizartinib or placebo added to induction and consolidation chemotherapy and/or allogeneic hematopoietic cell transplantation (allo-HCT), followed by maintenance, in newly diagnosed FLT3-ITD- negative acute myeloid leukemia (AML). This post hoc analysis assessed the impact of allo-HCT, modeled as a time-dependent variable, performed in first composite complete remission (CRc1) on overall survival (OS) and disease-free survival (DFS) according to treatment arm. Among 273 randomized patients, 32.2% in the quizartinib arm and 30.1% in the placebo arm underwent allo-HCT in CRc1. Quizartinib improved OS and DFS compared with placebo regardless of allo-HCT status. In Cox models with allo-HCT as a timedependent covariate, quizartinib remained associated with improved OS (HR 0.59; p=0.008) and DFS (HR 0.67; p=0.03), whereas allo-HCT was not significantly associated with OS (HR 0.91; p=0.62) and showed a numerical DFS benefit (HR 0.73; p=0.08). Multivariable analyses confirmed quizartinib as an independent favorable factor for OS (HR 0.56; p=0.046) and DFS (HR 0.60; p=0.04). No additional safety signals were observed. In patients with newly diagnosed FLT3-ITD-negative AML achieving CRc1, quizartinib improved OS and DFS in the overall population. Notably, the clinical benefit of quizartinib was observed regardless of allo-HCT, and appeared more evident in patients who did not proceed to transplant.