FLT3-ITD–mutated acute myeloid leukemia (AML) is an aggressive disease usually resistant to available treatment options, resulting in high front-line response rates but short response durations and low survival rates. Quizartinib—a potent selective FLT3 inhibitor—can work synergistically with venetoclax in AML cell lines and laboratory models.
In a phase I/II trial presented by Yilmaz et al at the European Hematology Association (EHA) 2022 Congress (Abstract S127), researchers evaluated the safety and efficacy of a triplet combination of venetoclax, quizartinib, and decitabine—a hypomethylating chemotherapy drug—in 28 patients with FLT3-ITD–mutated AML. Twenty-three had relapsed or refractory disease, and five patients were newly diagnosed.
The complete response rate was 78% for patients with relapsed or refractory disease, with a median overall survival of 7.6 months; the complete response rate was 100% for newly diagnosed patients, with a median overall survival of 14.5 months. Patients with underlying RAS/MAPK mutations had the lowest response rates (40%) compared to those without (94%), suggesting these mutations may drive resistance.
The most common grade 3 or 4 side effects included lung infections (42%) and neutropenic fever (30%).
The findings suggest this combination warrants further study for patients with FLT3-ITD–mutated AML.
Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.
