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ASH 2022 | Further analysis of QuANTUM-First: the impact of allo-HCT combined with quizartinib in FLT3-ITD+ AML

Harry Erba, MD, PhD, Duke University, Durham, NC, outlines results from a further analysis of the QuANTUM-First trial (NCT02668653) evaluating the impact of allogeneic hematopoietic cell transplantation (allo-HCT) in addition to quizartinib on the clinical outcomes of patients with FLT3-ITD+ acute myeloid leukemia (AML). Utilizing a PCR measurable residual disease (MRD) assay, results indicated that those receiving quizartinib were found to have undetectable FLT3-ITD. Furthermore, in patients undergoing allo-HCT, longer survival was observed in those treated with quizartinib versus placebo. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.

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Transcript (edited for clarity)

So quizartinib is a type two second-generation FLT3 inhibitor, which means it will only inhibit the FLT3-ITD. Now the FLT3-ITD mutation is actually the mutation that’s associated with a poor prognosis. Even though the current ELN stratification has reduced the FLT3 regardless of allelic burden to intermediate risk, we know these patients have a very high risk of relapse. Especially when combined with other mutations such as NPM1 and DNA methyltransferase 3A...

So quizartinib is a type two second-generation FLT3 inhibitor, which means it will only inhibit the FLT3-ITD. Now the FLT3-ITD mutation is actually the mutation that’s associated with a poor prognosis. Even though the current ELN stratification has reduced the FLT3 regardless of allelic burden to intermediate risk, we know these patients have a very high risk of relapse. Especially when combined with other mutations such as NPM1 and DNA methyltransferase 3A.

It is a more potent inhibitor of FLT3. A more specific inhibitor as a second generation than the currently available midostaurin for patients with newly diagnosed AML in combination with chemotherapy. The QuANTUM-First study aimed to show if the addition of a more potent and specific FLT3 inhibitor, such as quizartinib, to a backbone of standard induction, consolidation, and maintenance, including maintenance following allogeneic transplant in first remission, would improve on outcomes.

I presented the results of QuANTUM-First at the plenary session, the presidential session at EHA in 2022 in Austria. And the primary endpoint of the study was reached with an improvement in the median survival of patients receiving quizartinib compared to placebo with a hazard ratio of 0.776 that was statistically significant. We believe that this survival benefit was based on the observation that the duration of remissions we were seeing in the quizartinib arm were longer than with placebo. The cumulative incidence of relapse in the quizartinib arm was lower compared to placebo being around 31%. And what we’re showing at this year’s congress is that Mark Levis is showing MRD data looking at a very specific FLT3-ITD PCR MRD assay, where we show that more patients who received quizartinib had a completely undetectable FLT3-ITD by this PCR assay than patients receiving placebo. And there was a threefold lower median in the FLT3-ITD allelic ratio that was found, or amount that was found.

Richard Schlenk, the co-chair of the steering committee with me for QuANTUM-First, is presenting our transplant data. And the important news here is that patients who received quizartinib and then went on to a transplant, compared to patients who received placebo and went on to a transplant, those receiving quizartinib had an improvement in survival. But in general, as was shown in the first presentation, patients receiving quizartinib, regardless of transplant, actually were having a better overall survival.

So we still believe that at the current time, it’s very important for clinicians taking care of these patients to treat patients with… If they’re treating with a curative intent, to treat with intensive chemotherapy with a FLT3 inhibitor, currently midostaurin alone in the United States. Hopefully quizartinib soon. We can decide which one to choose for patients. But then moving on to an allogeneic stem cell transplant if at all possible in first remission.

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Disclosures

ImmunoGen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; MacroGenics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Covance (Abbvie): Consultancy, Other: Independent Review Committee, Research Funding; Janssen Oncology: Consultancy; Trillium Therapeutics: Consultancy; Takeda: Consultancy; Kura Oncology: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Gilead/Forty Seven: Research Funding; PTC therapeutics: Research Funding; ALX Oncology: Research Funding; Pfizer: Consultancy; Glycomimetics: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Celgene: Consultancy, Other, Speakers Bureau; Astellas Pharma: Consultancy; Amgen: Consultancy, Research Funding; Agios: Consultancy, Research Funding, Speakers Bureau; Abbvie: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau.