QuANTUM-First: Impact of Quizartinib and Allogeneic Transplant in First Remission in FLT3-ITD–Positive AML

Acute myeloid leukemia (AML) with FLT3-ITD mutation accounts for approximately 25% of newly diagnosed cases and is associated with poor prognosis, higher relapse risk, and reduced overall survival (OS). Although intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the standard of care in eligible patients, relapse risk remains high, ranging from 30% to 59% even after transplant. In this context, the second-generation selective FLT3 inhibitor quizartinib has emerged as a strategy to reduce relapse and prolong OS, leading to the design of the phase III QuANTUM-First trial.

QuANTUM-First was a randomized clinical trial that included 539 patients with FLT3-ITD–positive AML, assigned to receive standard chemotherapy with either quizartinib or placebo, followed by consolidation, allo-HCT, and maintenance therapy with the study drug according to initial randomization. Patients could undergo allo-HCT after achieving complete remission (CR) or composite complete remission (CRc), considered protocol-specified transplants. A post-hoc analysis assessed the impact of allo-HCT in first remission (CR1/CRc1) and its interaction with quizartinib use on overall survival.

The safety profile was consistent with what had previously been described for quizartinib. Hematologic, gastrointestinal, and infectious adverse events were more frequent in the active arm but were manageable. Among patients undergoing allo-HCT, the most common complications were graft-versus-host disease (GvHD) grade ≥2, as expected. Importantly, no new safety signals were identified, and the incidence of GvHD was comparable to previous allo-HCT studies.

Regarding efficacy, both quizartinib use and allo-HCT in CR1/CRc1 were independently associated with improved OS. Multivariate analyses showed significant reductions in risk of death: HR=0.553 for quizartinib and HR=0.527 for allo-HCT in CR1, as well as HR=0.645 and HR=0.557 for quizartinib and allo-HCT in CRc1, respectively. These findings suggest that combining the drug with early transplant enhances survival gains.

The QuANTUM-First data confirm that the combination of quizartinib with standard chemotherapy, followed by maintenance and incorporating allo-HCT in first remission, represents an effective and well-tolerated strategy for patients aged 18 to 75 years with FLT3-ITD–positive AML. The treatment consistently reduced the risk of death and relapse, without introducing new safety signals, consolidating quizartinib’s role as a key component of the therapeutic management of this population.

#AcuteMyeloidLeukemia #FLT3Mutation #Quizartinib #AllogeneicTransplant #LeukemiaResearch

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