FDA Grants Expedited Approval to Quizartinib for Patients With Newly Diagnosed AML With FLT3/ITD Mutations

On July 20, 2023, the Food and Drug Administration (FDA) approved quizartinib with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive, as detected by an FDA-approved test.

Priority review, fast-track designation, and orphan drug designation were granted for this regulatory decision. The FDA also approved the LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic test. 

The efficacy and safety of quizartinib plus chemotherapy was evaluated in the randomized, double-blind, placebo-controlled QuANTUM-First trial. The trial included 539 patients with newly diagnosed FLT3-ITD positive AML, where the FLT3-ITD status was determined prospectively with a clinical trial assay, and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.

In the trial, patients were randomized on a 1-to-1 basis to receive quizartinib (n = 268) or placebo (n = 271) with induction and consolidation therapy and as maintenance monotherapy according to the initial assignment. There was no re-randomization at the initiation of post-consolidation therapy. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) initiated maintenance therapy after HSCT recovery.

The main efficacy outcome measure for this trial was overall survival (OS), measured from randomization date until death. The primary analysis was conducted after a minimum follow-up of 2 years after the last patient was randomized. The trial demonstrated a statistically significant improvement in OS for the quizartinib arm [hazard ratio (HR) 0.78; 95% confidence interval [CI], 0.62 to 0.98; 2‑sided P = .0324]. The complete response (CR) rate in the quizartinib arm was 55% (95% CI, 48.7 to 60.9) with a median duration of 38.6 months (95% CI, 21.9 to not evaluable), and the CR rate in those receiving placebo was 55% (95% CI, 49.2 to 61.4) with a median duration of 12.4 months (95% CI, 8.8 to 22.7).

The approval noted that quizartinib is not indicated as maintenance monotherapy following allogeneic HSCT, and that no improvement in OS with quizartinib has been shown in those cases. Boxed warnings for quizartinib include QT prolongation, torsades de pointes, and cardiac arrest. Notably, quizartinib is available only through a restricted program, the Vanflyta Risk Evaluation and Mitigation Strategy (REMS). 

Source:

FDA approves quizartinib for newly diagnosed acute myeloid leukemia. Press Release. The US Food and Drug Administration. Published online July 20, 2023. Accessed July 24, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia