A phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia
Abstract
Abstract Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT. We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multikinase inhibitor dasatinib in adult patients with CBF-AML. Patients received “3+7” induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg daily on days 8 to 21 in induction, and on days 6 to 28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg daily. Primary end point was event-free survival (EFS). Secondary end points included overall survival, relapse-free survival, and cumulative incidence of relapse. A total of 202 patients were randomly assigned to the standard arm (n = 102) and to the dasatinib arm (n = 100). Median age was 49 years (range, 18-77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); and 58 (28.7%) patients had a KIT comutation. There was no statistically significant difference in EFS (hazard ratio, 0.92; 95% confidence interval, 0.63-1.33; P = .66) or secondary end points between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%). In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.ClinicalTrials.gov as NCT02013648.
Article Details
Authors (32)
Hartmut Döhner
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Daniela Späth
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Maral Saadati
Walter Fiedler
Katharina Götze
4Department of Medicine III, Hematology and Medical Oncology, Technical University of Munich, Munich, Germany
Elisabeth Koller
5Department of Internal Medicine III, Hanuschkrankenhaus Wien, Vienna, Austria
Jörg Westermann
6Department of Hematology, Oncology, and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
Wichard Vogel
7Department of Hematology and Oncology, Eberhard-Karls University, Tübingen, Germany
Michael Heuser
Michael Lübbert
10Department of Medicine I, Medical Center–University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Hans-Joachim Tischler
11Department of Hematology and Oncology, University Hospital of Minden, Minden, Germany
Ulrich Germing
Lino L. Teichmann
Lars Fransecky
14Department of Internal Medicine II, University Hospital Schleswig Holstein, Campus Kiel, Kiel, Germany
Albert Wölfler
15Division of Hematology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
David Nachbaur
16Internal Medicine V, Hematology and Oncology, Medical University of Innsbruck, Innsbruck, Austria
Bernd Hertenstein
17Department of Hematology and Oncology, Klinikum Bremen-Mitte, Bremen, Germany
Roland Schroers
18Medical Clinic II-Hematology and Oncology, Ruhr-University Bochum, Bochum, Germany
Uwe Martens
19Department of Hematology and Oncology, SLK-Clinics Heilbronn GmbH, Heilbronn, Germany
Stephanie von Harsdorf
20Klinik für Hämatologie, Onkologie & Stammzelltransplantation, Evangelische Kliniken Essen-Mitte, Essen, Germany
Markus Radsak
1Department of Hematology and Oncology, Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
Gregor Aschauer
22Internal Medicine I, Medical Oncology, Hematology and Gastroenterology, Barmherzige Schwestern Hospital, Linz, Austria
Stefanie Weißhaar
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Andrea Corbacioglu
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Anika Schrade
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Verena I. Gaidzik
1Department of Internal Medicine III, University Hospital of Ulm, Ulm, Germany
Felicitas Thol
Peter Paschka
23Klinikum der Stadt Ludwigshafen am Rhein, Medizinische Klinik A, Ludwigshafen am Rhein, Germany
Lars Bullinger
Axel Benner
Konstanze Döhner
12University Hospital of Ulm, Ulm, Germany
Arnold Ganser
8Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany