Exploring Alternative FLT3 Inhibitors for AML

Commentary
Video

Harry Erba, MD, PhD, discusses the recent quizartinib plus chemotherapy approval from the FDA for patients with newly-diagnosed FLT3-internal tandem duplication-positive acute myeloid leukemia.

Harry Erba, MD, PhD, professor of medicine at Duke Cancer Institute, discusses the recent quizartinib (Vanflyta) plus chemotherapy approval from the FDA for patients with newly-diagnosed FLT3-internal tandem duplication (ITD)-positive acute myeloid leukemia (AML).

In July 2023, the FDA granted approval to the combination of quizartinib 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 AML that is FLT3-ITD positive, as detected by an FDA-approved test.

Findings from the phase 3 QuANTUM-First trial (NCT02668653) supported this regulatory decision as findings revealed that patients given the quizartinib-based regimen had a statistically significant and clinically meaningful improvement in overall survival (OS) vs patients treated with chemotherapy plus placebo (HR, 0.78; 95% CI, 0.62-0.98; 2-sided P =.0324). The agent was also studied in the QuANTUM-R trial (NCT02039726) in this patient population.

Erba notes the importance of having options for patients with FLT3-mutated AML and suggests that some patients who don't respond to one FLT3 inhibitor might respond to a different one, even if they have the same mutations. This could be due to different tolerances or pharmacologic properties of the drugs.

Transcription:

0:09 | Quizartinib is a very potent, very selective inhibitor of FLT3 wild-type and FLT3-ITD mutations. There are a number of places that it can be used outside of, or considered, I should say, outside of the labeled indication. In fact, you might remember the QuANTUM-R study that was led by our colleague, Jorge E. Cortes, MD, showed an improvement in survival with quizartinib as a single agent, compared with standard of care salvage therapies for patients with relapsed or refractory FLT3-ITD mutated AML.

0:45 | Of course, we have gilteritinib [Xospata] available for those patients, which is active against both FLT3-ITD and TKD, but it may be conceivable that there will be patients failing to respond to 1 FLT3 inhibitor, [and they] may somehow respond to a different one. Maybe not based on mutations but on tolerance or pharmacologic properties.

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