Quizartinib in older patients (aged ≥60 years) with newly diagnosed FLT3-ITDpositive acute myeloid leukemia: subgroup analyses from QuANTUM-First

Abstract

The QuANTUM-First trial (NCT02668653) showed quizartinib significantly improved overall survival (OS) versus placebo when added to standard chemotherapy and as maintenance monotherapy in patients with newly diagnosed, FMS-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD)–positive acute myeloid leukemia. These post hoc analyses further evaluated clinical outcomes in older patients (≥60 years). Median OS was 17.5 and 14.2 months with quizartinib (n=107) and placebo (n=109), respectively (hazard ratio [HR], 0.91; 95% confidence interval [CI]: 0.66–1.26). Complete remission rates were similar (quizartinib, 53%; placebo, 55%), but median duration of complete response was numerically longer with quizartinib (15.9 vs. 9.0 months; HR, 0.92; 95% CI: 0.59–1.42). Cumulative incidence of relapse at 24 months was lower (quizartinib, 44%; placebo, 51%) and relapse-free survival was numerically longer (median, 16.6 vs. 9.7 months; HR, 0.91; 95% CI: 0.59–1.42) with quizartinib. NPM1 (quizartinib 62%, placebo 61%) and DNMT3A (51% and 50%) mutations were common and often co-mutated together (NPM1+DNMT3A; 38% and 38%), with each mutation or combination associated with numerically longer median OS with quizartinib (vs. placebo): 25.8 versus 15.4 (NPM1), 15.6 versus 11.5 (DNMT3A), and 21.8 versus 9.7 months (NPM1+DNMT3A), respectively. Quizartinib showed manageable tolerability for older patients, with safety generally similar to the placebo arm. Higher frequency of gastrointestinal treatmentemergent adverse events and a longer time to hematologic recovery were observed with quizartinib. ClinicalTrials.gov Identifier: NCT02668653.