FDA approves Vanflyta for newly diagnosed acute myeloid leukemia
The FDA approved quizartinib for use in combination with standard chemotherapy for treatment of patients with newly diagnosed acute myeloid leukemia with FLT3 internal tandem duplication mutations.
The indication authorizes use of quizartinib (Vanflyta, Daiichi Sankyo) with cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy after consolidation chemotherapy.
The FDA also approved LeukoStrat CDx FLT3 Mutation Assay (Quest Diagnostics) as a companion diagnostic to identify patients who may benefit from quizartinib.
Quizartinib is an orally administered selective FLT3 inhibitor.
Approximately 25% of AML cases have FLT3-internal tandem duplication (ITD) mutations. These mutations are associated with unfavorable prognosis — including higher risk for relapse and shorter OS — than FLT3-ITD wild-type disease.
Patients who received quizartinib plus intensive chemotherapy had an approximate doubling of their median OS, representing about a 22% reduction in risk for death, according to Mikkael Sekeres, MD, chief of the division of hematology in the leukemia section at University of Miami Sylvester Comprehensive Cancer Center and chair of ASH’s communications committee.
“Those are big numbers for a patient who has a FLT3 mutation,” he told Healio.
Moreover, front-line therapy with quizartinib plus chemotherapy has demonstrated an OS advantage among older adults with FLT3-postive AML, he added.
"[This approval] gives us a really good option for patients with the FLT3-ITD mutation and for older adults,” he said. “It also represents a good option for those patients who may not tolerate midostaurin.”
The FDA based approval of quizartinib on results of the randomized phase 3 QuANTUM-First trial, which included 539 adults (median age, 56 years) with newly diagnosed FLT3-ITD-positive AML.
Researchers randomly assigned patients 1:1 to quizartinib (n = 268) or placebo (n = 271) in combination with standard anthracycline- and cytarabine-based induction and consolidation regimens, plus maintenance monotherapy.
Eligible patients — including those who underwent allogeneic hematopoietic stem cell transplantation — received single-agent quizartinib or placebo for up to 36 cycles.
OS served as the primary endpoint. Secondary endpoints included EFS, post-induction rates of complete remission and composite complete remission, and the percentage of patients who achieved complete remission or composite complete remission with FLT3-ITD minimal residual disease negativity.
Median follow-up was 39.2 months.
As Healio previously reported, results showed improved OS in the quizartinib group (median, 31.9 months vs. 15.1 months; HR = 0.78; 95% CI, 0.62-0.98). Researchers reported the same complete response rate in each treatment group (55%) but a longer median response duration in the quizartinib group (38.6 months vs. 12.4 months).
Grade 3 or higher neutropenia occurred more frequently with quizartinib (18.1% vs. 8.6%), and a higher percentage of patients assigned quizartinib discontinued treatment due to adverse events (20.4% vs. 8.6%). Researchers reported mortality-associated treatment-emergent adverse event rates of 11.3% with quizartinib vs. 9.7% with placebo.
The FDA previously granted priority review to quizartinib for this indication. However, the agency subsequently extended its target action date by 3 months due to updates to proposed Risk Evaluation and Mitigation Strategies for the agent.
The label will include a boxed warning about QT prolongation, torsades de pointes and cardiac arrest.
Quizartinib is not indicated as maintenance monotherapy after allogeneic HSCT and OS improvement with the agent has not been demonstrated in that setting, according to FDA.