EHA 2023 | QuANTUM-First: FLT3-ITD-specific MRD clearance is associated with improved OS in newly diagnosed AML

Just as a preface to answering your question, QuANTUM-First is a frontline study combining the FLT3 inhibitor quizartinib with intensive induction chemotherapy, consolidation and maintenance, and allowed for transplant during the study without going off study – so patients who went to transplant were able to receive maintenance therapy thereafter. During this study, we collected measurements of patient’s disease burden, not just by morphology and looking under the microscope, but also by an assay that used both PCR and next-generation sequencing to quantify how much FLT3-ITD was present, as this study only enrolled patients with FLT3-ITD mutation. And we measured that at the end of induction, we measured that for patients prior to transplant and at various points thereafter. And what we found, not surprisingly, is that patients who were MRD-negative on the study had improved survival. And that’s been shown for a lot of different ways to measure MRD, but this was really one of the first studies, if not the first study, that looked at the role of FLT3 inhibitor in modulating survivals for patients with newly diagnosed AML treated intensively, and really not only confirmed the benefit of measuring FLT3-ITD as that measure of MRD, but also that there could be a role for a targeted inhibitor to potentially deepen the response and with that predict long term survival. Indeed, we found more patients who were MRD-undetectable in the quizartinib arm, about two-fold more patients – it was like 11% versus 22%, something like that – and the median level of MRD was lower in the quizartinib arm.