Quizartinib Enhances Survival in FLT3-ITD+ AML With Deep MRD Reduction

Quizartinib significantly improves long-term survival in FLT3-ITD+ acute myeloid leukemia (AML) by achieving deep and sustained reductions in measurable residual disease (MRD), according to the phase III QuANTUM-First trial presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

To determine the impact of FLT3-ITD-specific MRD on patient outcomes, the investigators randomized 539 patients to receive either quizartinib or placebo in addition to intensive chemotherapy and maintenance monotherapy. Genomic DNA was collected from patients at remission after induction and after consolidation (pretransplant for those who received hematopoietic cell transplantation). An FLT3-ITD polymerase chain reaction for next-generation sequencing assay was used to measure ITD mutations. MRD was classified with two thresholds: undetectable (<0) and MRD– (predefined 10–4 cutoff).

Of the 539 patients, 368 (68.3%) achieved composite complete remission (CRc). MRD analysis was performed on 321 of those patients during induction and on 337 at the end of consolidation.

The CRc rates with ITD MRD <10–4 were similar between the quizartinib and placebo arms (25.4% vs 21.8%, respectively; P=0.3430). However, a greater proportion of patients on quizartinib had undetectable MRD (0 cutoff) at the end of induction (12.3% vs 7.0%; P=0.0403).

For patients with CRc after induction, the median best ITD variant allele frequency by the end of consolidation was lower in the quizartinib group compared with the placebo group (0% vs 0.0017%; P=0.0006).

With the undetectable ITD cutoff at the end of induction, quizartinib improved OS compared with placebo, regardless of MRD status (hazard ratio, 0.79 in MRD−; 0.75 in MRD+). In MRD+ patients, the median OS was not reached with quizartinib, compared with 35.4 months with placebo. Similar results were observed with the MRD– cutoff of 10^–4.

“These findings demonstrate the prognostic utility of ITD-specific MRD measurements in the management of patients with FLT3-ITD+ AML and suggest that long-term OS benefits with quizartinib derive in part from a deep and sustained reduction of FLT3-ITD,” the researchers concluded.

Reference

Perl A, Brulc E, Herba HP, et al. QuANTUM-First trial: FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD)–specific measurable residual disease (MRD) clearance assessed through induction and consolidation is associated with improved overall survival (OS) in newly diagnosed (ND) FLT3-ITD+ AML patients. Abstract #AML-197. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.