QuANTUM-First was a randomized trial that demonstrated that the addition of quizartinib, a potent and selective FLT3 inhibitor, to induction and consolidation chemotherapy, followed by monotherapy maintenance, improved the survival for patients with newly diagnosed FLT3-ITD (FMS-like tyrosine kinase 3‒internal tandem duplication)--mutated acute myeloid leukemia (AML). We conducted a post-hoc analysis of the trial data focusing on measurable residual disease (MRD) as assayed using an amplicon-based next-generation sequencing assay and on the impact of molecular biomarkers such as FLT3-ITD insertion length and co-mutations. This is the first prospective, randomized trial of a FLT3 inhibitor in newly diagnosed patients in which FLT3-ITD MRD data were collected throughout therapy. We established that quizartinib induces deeper remissions with respect to FLT3-ITD MRD vs placebo, and that the amount of MRD at the completion of induction correlates with relapse and survival. We found that longer FLT3-ITD insertion mutations correlated with worse outcome, quizartinib was beneficial irrespective of insertion mutation length, and the FLT3-ITD MRD assay was more sensitive when bone marrow was used vs peripheral blood. Regardless of the presence of NPM1 co-mutation, quizartinib increased the rates of MRD-negative patients at the end of induction vs placebo. Finally, comparison of the FLT3-ITD mutation length between the polymerase chain reaction (PCR) with capillary electrophoresis assay obtained at screening and the PCR next-generation sequencing MRD assay performed at the end of induction showed a 96.2% concordance with the exact ITD length. This trial was registered at www.ClinicalTrials.gov as NCT02668653.

1 State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Haihe Laboratory of Cell Ecosystem Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin 300020 China; 2 Tianjin Institutes of Health Science Tianjin 301600 China Tianjin China

Abramson Cancer Center University of Pennsylvania Philadelphia Pennsylvania United States

Catholic Hematology Hospital Seoul St Mary's Hospital College of Medicine The Catholic University of Korea Seoul Korea Republic of

Chang Gung Memorial Hospital Taipei Taiwan

Daiichi Sankyo Basking Ridge New Jersey United States

Daiichi Sankyo Inc Basking Ridge New Jersey United States

Duke University Durham North Carolina United States

Georgia Cancer Center Augusta Georgia United States

Hospital Universitari i Politècnic La Fe Valencia Spain

Institute of Hematology and Transfusion Medicine Warsaw Poland

Johns Hopkins University Baltimore Maryland United States

NCT Clinical Trial Center Heidelberg Germany

Paris Saint Louis Leukemia Institute Université Paris Cité Hôpital Saint Louis Assistance Publique Hôpitaux de Paris Paris France

Sylvester Comprehensive Cancer Center University of Miami Miller School of Medicine Miami Florida United States

University Hospital Centre Zagreb Zagreb Croatia Republic of

University Hospital Hradec Kralove Hradec Kralove Czech Republic

University of Rome Tor Vergata Rome Italy

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ClinicalTrials.gov
NCT02668653