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

05/01/2026

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

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.

PMID: 41490515