QuANTUM-First (ClinicalTrials.gov identifier: NCT02668653) was a randomized phase III trial in patients with newly diagnosed FLT3-internal tandem duplication (ITD)-positive acute myeloid leukemia (AML) treated with quizartinib or placebo plus standard induction and consolidation chemotherapy and/or allogeneic hematopoietic cell transplantation (allo-HCT), followed by single-agent maintenance therapy. We evaluated the impact of allo-HCT performed in first complete remission (CR1) or composite CR1 (CRc1) on overall survival (OS), considering treatment randomization. Post-hoc extended Cox regression multivariable analyses were conducted in patients who achieved complete remission/composite complete remission by the end of induction, including allo-HCT in CR1/CRc1 as a time-dependent variable to identify prognostic and predictive factors for OS. There were 297 patients with complete remission by the end of induction (quizartinib, N=147; placebo, N=150); of these, 157 (52.9%) underwent allo-HCT in CR1 (quizartinib, N=84; placebo, N=73). There were 368 patients with composite complete remission by the end of induction (quizartinib, N=192; placebo, N=176); of these, 196 (53.3%) underwent allo-HCT in CRc1 (quizartinib, N=110; placebo, N=86). Multivariable analyses revealed quizartinib treatment and allo-HCT in either CR1 (hazard ratio [HR]=0.553, 95% confidence interval [95% CI]: 0.383-0.798, P=0.0015 and HR=0.527, 95% CI: 0.349-0.796, P=0.0023, respectively) or CRc1 (HR=0.645, 95% CI: 0.470‒0.886, P=0.0068 and HR=0.557, 95% CI: 0.391-0.793, P=0.0012, respectively) as significant predictive factors for a longer OS. No new safety signals were identified. Patients who underwent protocol-specified allo-HCT in CR1/CRc1 experienced post-transplant-related complications, mostly grade ≥2 graft-versus-host disease, as expected. This post-hoc analysis further supports the use of quizartinib and allo-HCT in CR1/CRc1 as an efficacious and well-tolerated treatment strategy for newly diagnosed FLT3-ITD-positive AML patients fit for intensive chemotherapy.

Chang Gung Medical Foundation Linkou

Daiichi Sankyo Inc Basking Ridge NJ

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

Department of Internal Medicine Haematology University Hospital Hradec Kralove Hradec Kralove Czechia

Division of Hematologic Malignancies Johns Hopkins University Baltimore MD

Division of Hematology Oncology University of Pennsylvania Philadelphia PA

Division of Hematology University Hospital Centre Zagreb Zagreb Croatia

Duke Cancer Institute Durham NC

Georgia Cancer Center at Augusta University Medical Center Augusta GA

Hematology Department La Fe University and Polytechnic Hospital Valencia

Hopital Saint Louis Assistance Publique Hopitax de Paris Universite Paris Cite

Institute of Hematology and Blood Diseases Hospital Tianjin

Institute of Hematology and Blood Transfusion Warsaw

National Center of Tumor Diseases Trial Center German Cancer Research Center and Heidelberg University Hospital Heidelberg Germany; Department of Internal Medicine 5 Heidelberg University Hospital Heidelberg

Sylvester Cancer Center University of Miami Health System Miami FL

Tor Vergata Polyclinic Hospital Rome Rome

University Hospital Virgen de las Nieves Granada

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ClinicalTrials.gov
NCT02668653