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

Clinical Snapshot

Key Findings

• P Value: P = 0.66

• Effect Size: Hazard ratio 0.92 favouring dasatinib arm

• Primary Outcome: Event-free survival showed no significant difference between arms

• Nnt Or Sensitivity: No number needed to treat calculable due to lack of efficacy

• Confidence Interval: 95% CI 0.63-1.33

Clinical Application

Standard intensive chemotherapy protocols are readily available in Australian tertiary centres; dasatinib addition would require additional monitoring and cost Results support current ALLG and NCCN guidelines recommending intensive chemotherapy alone for CBF-AML. Dasatinib not PBS-listed for AML indication. TGA approval would be required for this specific use Adults with newly diagnosed CBF-AML suitable for intensive chemotherapy, particularly those with t(8;21) or inv(16)/t(16;16) cytogenetics

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.

References

1. 1.Döhner, H., Späth, D., Saadati, M., Fiedler, W., Götze, K., Koller, E., Westermann, J., Vogel, W., Heuser, M., Lübbert, M., Tischler, H.-J., Germing, U., Teichmann, L. L., Fransecky, L., Wölfler, A., Nachbaur, D., Hertenstein, B., Schroers, R., Martens, U., von Harsdorf, S., Radsak, M., Aschauer, G., Weißhaar, S., Corbacioglu, A., Schrade, A., Gaidzik, V. I., Thol, F., Paschka, P., Bullinger, L., Benner, A., Döhner, K., & Ganser, A. (2026). A phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia. Blood. https://doi.org/10.1182/blood.2025030722