Quizartinib in newly diagnosed patients with FLT3-ITD-positive AML who received maintenance therapy in QuANTUM-First.

QuANTUM-First (NCT02668653) demonstrated improved overall survival (OS) in FLT3-ITD-positive patients with newly diagnosed acute myeloid leukemia (ndAML) treated with quizartinib plus standard chemotherapy. Herein, we evaluated the impact of post-consolidation/post-transplant single-agent maintenance therapy on clinical outcomes in patients receiving maintenance, focusing on measurable residual disease (MRD) status at maintenance onset. Overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were prespecified exploratory analyses. Cumulative incidence of relapse (CIR), analyses by allogeneic hematopoietic stem cell transplant (allo-HCT), and analyses by MRD status were post-hoc and not powered for statistical significance. Samples for FLT3-ITD MRD analysis were collected in composite complete remission patients ≤30 days before receiving maintenance and assessed by an ultrasensitive amplicon-based assay. More transplanted quizartinib-treated patients received maintenance (71%) vs placebo (55%); OS benefit was not demonstrated among these patients. In patients who did not undergo allo-HCT, quizartinib maintenance was associated with a significant OS benefit (HR 0.401; 95% CI, 0.192-0.838), including a benefit in patients who were MRD-negative at the start of maintenance (OS HR of 0.194, 95% CI, 0.056-0.676). Patients who were MRD-negative at the completion of consolidation achieved 89.1% (95% CI, 70.0%-96.4%) survival at 3 years with quizartinib maintenance in the absence of allo-HCT. These data suggest that for patients who achieve FLT3-ITD MRD negativity after induction and consolidation with quizartinib, maintenance with quizartinib provides a significant survival benefit and in some patients may eliminate the need for allo-HCT.