QUIWI phase II post hoc analysis: Quizartinib and allo-HSCT in ND FLT3-ITD-negative AML

Results from a post hoc analysis of the randomized, double-blind, placebo-controlled phase II QUIWI (NCT04107727) trial, evaluating quizartinib (n = 180) or placebo (n = 93) + chemotherapy ± allogeneic hematopoietic stem cell transplantation (allo-HSCT), followed by single-agent maintenance therapy, in patients with newly diagnosed (ND) FLT3-internal tandem duplication (ITD)-negative acute myeloid leukemia (AML), were published in Haematologica by Lloret-Madrid et al. The primary endpoint was overall survival (OS). Additional endpoints included disease-free survival (DFS), duration of response (DoR), and cumulative incidence of relapse (CIR).

Key data: At a median follow-up of 40.5 months, the OS among patients in first composite complete remission (CRc1) was numerically longer with quizartinib vs placebo in those who received allo-HSCT (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.28–1.25; p = 0.1638) and those who did not receive allo-HSCT (HR, 0.59; 95% CI, 0.33–1.04; p = 0.636). Numerical improvements in DFS were observed with quizartinib vs placebo in patients who received allo-HSCT in CRc1 (HR, 0.8; 95% CI, 0.39–1.63; p = 0.5407) and significant improvements in DFS were observed with quizartinib in patients in CRc1 who did not undergo allo-HSCT (HR, 0.61; 95% CI, 0.36–0.98; p = 0.04). In Cox models with allo-HSCT as a time-dependent covariate, quizartinib significantly improved OS (HR, 0.59; 95% CI, 0.40–0.87; p = 0.008) and DFS (HR, 0.67; 95% CI, 0.48–0.95, p = 0.03) vs placebo. Multivariable analyses revealed quizartinib as an independent factor improving OS (HR, 0.56; 95% CI, 0.31–0.99; p = 0.046) and DFS (HR, 0.60; 95% CI, 0.38–0.97; p = 0.04).

Key learning: Quizartinib was associated with improvements in OS and DFS compared with placebo in patients with ND FLT3-ITD-negative AML in CRc1, regardless of allo-HSCT.