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Publications

Journal Article Ahead of print

PubMed: 41490515 DOI: 10.1182/blood.2025030722

Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia.

Blood

Authors: Hartmut Döhner, Daniela Späth, Maral Saadati, Walter Fiedler, Katharina S Götze, Elisabeth Koller, Jörg Westermann, Wichard Vogel, Michael Heuser, Michael Lübbert, Hans-Joachim Tischler, Ulrich Germing, Lino Lars Teichmann, Lars Fransecky, Albert Wölfler, David Nachbaur, Bernd Hertenstein, Roland Schroers, Uwe M Martens, Stephanie von Harsdorf, Markus P Radsak, Gregor Aschauer, Stefanie Weißhaar, Andrea Corbacioglu, Anika Schrade, Verena I Gaidzik, Felicitas R Thol, Peter Paschka, Lars Bullinger, Axel Benner, Konstanze Döhner, Arnold Ganser

Affiliations

  • University Hospital Ulm, Ulm, Germany.
  • University Hospital of Ulm, Ulm, Germany.
  • German Cancer Research Center, Germany.
  • Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany.
  • Technical University of Munich (TUM) School of Medicine, Munich, Germany.
  • Hanuschhospital, Vienna, Austria.
  • Charité-University Medical Center, Campus Virchow Clinic, Berlin, Germany.
  • UKT, Tübingen, Germany.
  • University Hospital Halle (Saale), Halle (Saale), Germany.
  • Medical Center - University of Freiburg, Freiburg, Germany.
  • University Hospital of Minden, Minden, Germany.
  • Heinrich-Heine-University, Düsseldorf, Germany.
  • University Hospital Bonn, Bonn, Germany.
  • Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
  • Medical University of Graz, Graz, Austria.
  • Innsbruck Medical University, Innsbruck, Austria.
  • Klinikum Bremen Mitte, Bremen, Germany.
  • Ruhr-Universität Bochum - Knappschaft-Kliniken, Bochum, Germany.
  • SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany.
  • Evangelische Kliniken Essen-Mitte, Essen, Germany.
  • University Medical Center, Mainz, Germany.
  • Barmherzige Schwestern Hospital, Linz, Austria.
  • Ulm University Hospital, Ulm, Germany.
  • Hannover Medical School, Hannover, Germany.
  • Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany.
  • Charité University Medicine, Berlin, Germany.
  • German Cancer Research Center, Heidelberg, Germany.

Abstract

BACKGROUND

Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT.

AIMS

We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multi-kinase inhibitor dasatinib in adult patients with CBF-AML.

METHODS

Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg QD on days 8-21 in induction, and on days 6-28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg QD. Primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival, relapse-free survival, and cumulative incidence of relapse.

RESULTS

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); 58 (28.7%) patients had a KIT co-mutation. There was no statistically significant difference in EFS (HR 0.92, 95%-CI 0.63, 1.33; p=0.66) or secondary endpoints 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%).

CONCLUSION

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.

MeSH

Core Binding Factors, Dasatinib, Incidence, Leukemia, Drug Therapy, Leukemia, Myeloid, Acute, Leukemia, Myeloid, Therapeutics, Mutation, Chemotherapy