FDA Approves Quizartinib Plus Chemotherapy for Newly-Diagnosed FLT3-ITD+ AML


Data from the phase 3 QuANTUM-First trial have led the FDA to approve quizartinib with or without standard chemotherapy for the treatment. of FLT3-ITD-mutant acute myeloid leukemia .

  • The FDA approval of quizartinib plus chmeotherapy for newly-diagnosed FLT3-internal tandem duplication (ITD)-posoitive acute myeloid leukemia (AML) follows a priority review, fast track designation and orphan drug designation.

  • No indication was approved for quizartinib as maintenance monotherapy following allogeneic hematopoietic stem cell transplant.

  • Along with quizartinib, the FDA granted approval to the LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic.

The FDA has granted approval to the combination of quizartinib (Vanflyta) and standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of adult patients with newly-diagnosed, FLT3-ITD-positive AML.1

Approval of quizartinib for this indication is supported by findings from the phase 3 QuANTUM-First trial (NCT02668653). The findings showed that quizartinib as monotherapy and in a combination following consolidation, led to a statistically significant and clinically meaningful improvement in overall survival (OS) vs chemotherapy alone in this patient population.1,2

The trial evaluated quizartinib combined with intensive chemotherapy as well as quizartinib as continuation monotherapy and showed that treatment with the agent was generally manageable and no new safety signals observed. Further data published in The Lancet showed that at a median follow-up of 39.2 months, patients treated with quizartinib achieved a median OS of 31.9 months (95% CI, 21.0–not estimable) vs 15.1 months (95% CI, 13.2-26.2) for those in the placebo arm, resulting in a 22.4% reduction in the risk of death (HR, 0.776; 95% CI, 0.615-0.979; 2-sided P = .0324).2

Both arms of the study had a similar rate of adverse events (AEs). Grade 3 or higher AEs occurred in 92% of the quizartinib-treated group compared with 90% of the placebo group. In both arms, febrile neutropenia, hypokalaemia, and pneumonia were the most common grade 3 or 4 AEs. The most common grade 3 or 4 AE in the quizartinib group was neutropenia.

Harry P. Erba, MD, PhD

Harry P. Erba, MD, PhD

“AML with FLT3-ITD mutation is associated with a very high risk of relapse following initial therapy; these patients should be considered for curative therapy at the time of diagnosis, if possible. The addition of quizartinib to standard induction and consolidation chemotherapy including allogeneic stem cell transplantation results in deeper remissions compared with intensive chemotherapy alone. These deeper remissions likely underlie the longer duration of remission, the lower cumulative incidence of relapse, and the improvement in both relapse free and overall survival observed with the addition of quizartinib to potentially curative AML therapy,” Harry Erba, MD, PhD, a hematologic oncologist anda professor of medicine and director of the Leukemia Program at Duke Health, told Taregted OncologyTM.

The international, randomized, double-blind, placebo-controlled QuANTUM-First enrolled patients with newly-diagnosed FLT3 ITD–positive AML who were aged 18 to 75 and who had at least a 3% FLT3 ITD allelic frequency. During the screening portion of the trial, patients began 7+3 chemotherapy.2,3

Patients were randomly assigned in a 1:1 fashion to receive either quizartinib at 40 mg on days 8 through 21 or placebo added to standard chemotherapy in the form of cytarabine on days 1 to 7 and daunorubicin or idarubicin on days 1 to 3 as induction treatment for up to 2 cycles.

Then, patients were given consolidation treatment with high-dose cytarabine in combination with quizartinib or placebo and/or transplant per institutional policies. Monotherapy with quizartinib or placebo was then given 1 time a day for up to 36 cycles.

The trials stratification factors included region (North America vs European Union vs Asia/other regions), patient age (< 60 years vs ≥ 60 years), and white blood cell count (< 40 x 109/L vs ≥ 40 x 109/L).Investigators assessed OS as the study's primary end point and event-free survival (EFS), complete remission (CR), composite CR (CRc), and safety as secondary end points. Relapse-free survival (RFS) and duration of CR were the exploratory end points of the study.

There were 3468 patients screened at the time of the data cutoff of August 13, 2021, and 539 of those patients underwent randomization. Two-hundred sixty-eight patients made up the quizartinib arm and 271 patients were in the placebo arm. Out of those patients, 265 and 268 received treatment, respectively. Baseline patient characteristics of patients were balanced between the arms. Median age among those enrolled was 56 years (range, 20-65) in both arms, approximately 54% were male, and most patients were White and from Europe.

“The approval of quizartinib marks a major advance in the treatment of people afflicted with this most aggressive form of AML,” added Erba.


1. FDA approves quizartinib for newly diagnosed acute myeloid leukemia. News release. July 20, 2023. Accessed July 20, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia

2. Erba HP, Monetesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients withFLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401(10388):1571-1583. doi: 10.1016/S0140-6736(23)00464-6

3. Quizartinib with standard of care chemotherapy and as continuation therapy in patients with newly diagnosed FLT3-ITD (+) acute myeloid leukemia (AML) (QuANTUM-First). ClinicalTrials.gov. Updated October 5, 2022. Accessed February 22, 2023. https://clinicaltrials.gov/ct2/show/NCT02668653

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