QuANTUM-First post hoc analysis: Impact of quizartinib on MRD in FLT3-ITD AML

The phase III QuANTUM-First trial (NCT02668653) has demonstrated improved survival with quizartinib, a selective FMS-like tyrosine 3 (FLT3) inhibitor. Results from a post hoc analysis of the QuANTUM-First trial, evaluating the impact of quizartinib on measurable residual disease (MRD) in patients with newly diagnosed FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML), were published by Levis et al. in Blood Advances. The analysis comprised MRD data from 321 patients (quizartinib, n = 162; placebo, n = 159) who achieved composite complete remission (CRc) by the end of induction.

Key data: Quizartinib was associated with a lower median best FLT3-ITD MRD variant allele frequency (VAF) vs placebo during induction (p = 0.0159) and consolidation (p = 0.0006). MRD negativity post-induction predicted better survival outcomes. Quizartinib showed consistent benefit across FLT3-ITD insertion mutation length. Concordance with exact internal tandem duplication (ITD) length at the end of induction was observed in 96.2% of patients who achieved CRc.

Key learning: Quizartinib led to deeper remissions and improved survival outcomes in MRD-negative patients with FLT3-ITD AML. These findings validate FLT3-ITD MRD status as a prognostic biomarker, supporting its use in guiding post-remission therapy and transplant decisions.