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Triplet Combination Therapy Yields High Response Rates in Patients With FLT3-Mutated AML


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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.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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