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FDA approves quizartinib for newly diagnosed FLT3-ITD AML

On July 20, 2023, the Food and Drug Administration (FDA) approved quizartinib for adult patients diagnosed with newly diagnosed FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD)-mutated acute myeloid leukemia (AML). The approval is for the use of quizartinib in combination with standard cytarabine and anthracycline induction, cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy. The LeukoStrat CDx FLT3 mutation assay has also been approved by the FDA as a companion diagnostic for quizartinib.1

Despite advancements in the AML space, survival rates remain stubbornly low, improving only marginally over the last few decades. The difficulty the malignancy presents can partly be attributed to its heterogeneity and the need for more targeted agents.2 FLT3-ITD represents the most common AML driver mutation, and presents with a high leukemic burden and a poor prognosis.3  Considering the poor outcomes in this patient population, several FLT3-inhibitors have emerged for this subgroup in the relapsed or refractory (R/R) setting, including sorafenib and midostaurin. Quizartinib is a more specific FLT3 inhibitor and has also been approved as salvage therapy in R/R FLT3-ITD AML.4

The approval of quizartinib in the frontline setting was based on the findings from the QuANTUM-First trial (NCT02668653), which was a randomized, double-blind, and placebo-controlled study involving 539 patients with newly diagnosed FLT3-ITD AML. FLT3-ITD status was prospectively determined using a clinical trial assay and later verified using the companion LeukoStrat CDx FLT3 mutation assay.1

Patients in the study were randomly assigned in a 1:1 ratio to receive either quizartinib (n=268) or placebo (n=271) in combination with induction and consolidation therapy, with quizartinib or placebo administered as maintenance monotherapy according to the initial assignment. Re-randomization at the initiation of post-consolidation therapy was not undertaken. For patients who proceeded to hematopoietic stem cell transplantation (HSCT), maintenance therapy was initiated after HSCT recovery.1

The primary efficacy outcome measure in the trial was overall survival (OS), which was measured from the date of randomization until death from any cause. The primary analysis was conducted after a minimum follow-up of 24 months from the last patient’s randomization. Quizartinib yielded statistically significant improvements in OS for patients in that arm [hazard ratio (HR) 0.78; 95% CI: 0.62, 0.98; 2‑sided p=0.0324].1

In addition to the improvement in OS, the complete response (CR) rate in the quizartinib arm was 55% (95% CI: 48.7, 60.9) with a median duration of 38.6 months (95% CI: 21.9, NE). In comparison, the CR rate for patients receiving placebo was 55% (95% CI: 49.2, 61.4) with a median duration of 12.4 months (95% CI: 8.8, 22.7). 1

We spoke to Harry Erba, MD, PhD, Duke University, Durham, NC on the QuANTUM-First trial. Dr Erba commented that the “results showed that when we use a type two second generation, more potent, more specific FLT3 inhibitor, that we can improve the survival of patients”.

Quizartinib is not indicated as maintenance monotherapy after allogeneic HSCT as quizartinib has not been demonstrated to improve OS in this setting. Quizartinib holds a boxed warning for notes QT prolongation, torsades de pointes, and cardiac arrest. Quizartinib is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Vanflyta REMS. 1

This landmark approval offers healthcare professionals a new and effective treatment option for adult patients with newly diagnosed FLT3-ITD-positive AML. Close monitoring and appropriate patient selection guided by the companion diagnostic LeukoStrat CDx FLT3 mutation assay will be essential in ensuring optimal outcomes with this therapy.

  1. U.S. Food and Drug Administration. FDA approves quizartinib for newly diagnosed acute myeloid leukemia. Available here (Accessed: 21/07/2023).
  2. Carter JL, Hege K, Yang J, et al. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy. Signal Transduction and Targeted Therapy. 2020 Dec 18; 5(1):288.
  3. Daver N, Schlenk RF, Russell NH. et al. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019 Jan 16; 33(2):299–312.
  4. Cao Y, Zhang C, Cao L. et al. Quizartinib is a good option for AML patients with FLT3-ITD mutations. The Innovation Medicine. 2023 Jun 8; 1(1):100007.

Written by Thomas Southgate

Edited by Elitsa Kamberska