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

FDA

The FDA has approved quizartinib (Vanflyta) in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3-ITD positive, as detected by an FDA-approved test.¹

The regulatory decision was supported by data from the phase 3 QuANTUM-First trial (NCT02668653), which demonstrated that those who received quizartinib experienced a statistically significant and clinically meaningful improvement in overall survival (OS) vs those given chemotherapy plus placebo (HR, 0.78; 95% CI, 0.62-0.98; 2-sided P = .0324).²

At a median follow-up of 39.2 months (interquartile range, 31.9-45.8), the median OS was 31.9 months (95% CI, 2.0–not estimable [NE]) with quizartinib vs 15.1 months (95% CI, 13.2-26.2) with placebo.

Moreover, the complete response (CR) rate in the quizartinib (95% CI, 48.7%-60.9%) and placebo (95% CI, 49.2%-61.4%) arms was 55%.¹ The median duration of this response in the investigative arm was 38.6 months (95% CI, 21.9-NE) vs 12.4 months (95% CI, 8.8-22.7) in the control arm.

“The approval of [quizartinib] represents a significant advancement for the treatment of patients with newly diagnosed FLT3-ITD–positive AML, which is one of the most aggressive and difficult-to-treat subtypes,” Harry P. Erba, MD, PhD, professor of medicine in the Department of Medicine of the Division of Hematologic Malignancies and Cellular Therapy at Duke Cancer Institute, stated in a news release.³ “In the QuANTUM-First trial, [quizartinib] added to standard chemotherapy and continued as maintenance resulted in longer remission and prolonged overall survival and it will be a much-needed new treatment option that has potential to change the way FLT3-ITD–positive AML is treated.”

The randomized, double-blind, placebo-controlled, QuANTUM-First trial enrolled 539 patients with newly diagnosed, FLT3-ITD–positive AML who had a FLT3-ITD allelic frequency of at least 3%.⁴ FLT3-ITD status was determined prospectively via a clinical trial assay and verified retrospectively by the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.¹

Patients were randomly assigned 1:1 to receive quizartinib or placebo in combination with induction and consolidation therapy, then as maintenance monotherapy. Randomization did not occur again at the initiation of post-consolidation therapy. In patients who underwent hematopoietic stem cell transplantation following consolidation, maintenance therapy was given after recovery from the transplant.

Regarding safety, the most common grade 3 or higher treatment-emergent adverse effects (TEAEs) occurring in at least 10% of patients enrolled in QuANTUM-First included febrile neutropenia (43.4% and 41.0% in the quizartinib and placebo arms, respectively), neutropenia (18% and 8.6%), hypokalemia (18.9% and 16.4%), and pneumonia (11.7% and 12.7%). Rates of TEAEs associated with fatal outcomes were 11.3% for quizartinib vs 9.7% for chemotherapy alone, and these deaths were mainly due to infections.⁵

Notably, quizartinib is not indicated as maintenance monotherapy following allogeneic HSCT, as an improvement in OS with quizartinib has not been demonstrated in this setting.¹

WATCH: Harry P. Erba, MD, PhD, of Duke Cancer Institute, discusses the significance of the FDA approval of quizartinib in combination with chemotherapy in patients with newly diagnosed FLT3-ITD–positive AML.

References

1. FDA approves quizartinib for newly diagnosed acute myeloid leukemia. News release. FDA. 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. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-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. Vanflyta first FLT3 inhibitor approved in the US specifically for patients with newly diagnosed FLT3-ITD positive AML. News release. Daiichi Sankyo. July 20, 2023. Accessed July 20, 2023. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202307/20230720_E.pdf
4. 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 December 29, 2022. Accessed July 20, 2023. https://clinicaltrials.gov/ct2/show/NCT02668653
5. Erba H, Montesinos P, Vrhovac R, et al. Quizartinib prolongs survival vs placebo plus intensive induction and consolidation therapy followed by single-agent continuation in patients aged 18-75 years with newly diagnosed FLT3-ITD+ AML. Presented at: 2022 EHA Congress; June 9-12, 2022; Vienna, Austria. Abstract S100.