Background
Phase 3 open-label randomized trial. 202 adult patients with core-binding factor (CBF) AML: 94 with t(8;21) and 108 with inv(16)/t(16;16). KIT co-mutation present in 58 patients (28.7%). Median age 49 years (range 18–77). Dasatinib was investigated based on KIT overexpression/mutation in CBF-AML and preclinical activity.
Interventions and follow up
Arm A: Standard "3+7" induction (idarubicin/daunorubicin + cytarabine) + 4 cycles high-dose cytarabine consolidation + dasatinib 100 mg daily (days 8–21 induction; days 6–28 each consolidation cycle) + 12 months single-agent dasatinib maintenance
Arm B: Standard "3+7" induction + 4 cycles high-dose cytarabine consolidation
Primary endpoint: Event-free survival (EFS)
Median follow up: NR (mature analysis)
Arm B: Standard "3+7" induction + 4 cycles high-dose cytarabine consolidation
Primary endpoint: Event-free survival (EFS)
Median follow up: NR (mature analysis)
Results
EFS: HR 0.92 (95% CI 0.63–1.33), P=.66 — no significant difference
Overall survival: no significant difference
Relapse-free survival: no significant difference
EFS in KIT-mutated subgroup: no significant difference
Overall survival: no significant difference
Relapse-free survival: no significant difference
EFS in KIT-mutated subgroup: no significant difference
Adverse events
Grade ≥3 serious AEs: 64% (Arm A, dasatinib) vs 36% (Arm B)
Dasatinib-associated toxicity: fluid retention, pleural effusion, and cytopenias
Safety profile: no new safety signals but a substantially increased grade ≥3 event burden
Dasatinib-associated toxicity: fluid retention, pleural effusion, and cytopenias
Safety profile: no new safety signals but a substantially increased grade ≥3 event burden
Conclusions
Adding dasatinib to intensive chemotherapy did not improve EFS, OS, or relapse-free survival in CBF-AML, including in patients with KIT mutations, and was associated with significantly higher toxicity without efficacy benefit.
Key Limitations
Design: open-label trial
Subgroups: KIT mutation prevalence (28.7%) may have been insufficient for a subgroup-powered analysis; mixed CBF subtypes (t(8;21) vs inv(16)) may have diluted subtype-specific effects
Exposure: intermittent dasatinib dosing during induction/consolidation followed by maintenance may not represent the optimal exposure strategy
Subgroups: KIT mutation prevalence (28.7%) may have been insufficient for a subgroup-powered analysis; mixed CBF subtypes (t(8;21) vs inv(16)) may have diluted subtype-specific effects
Exposure: intermittent dasatinib dosing during induction/consolidation followed by maintenance may not represent the optimal exposure strategy
Clinical Context
This trial confirms that dasatinib does not add benefit to standard CBF-AML therapy. CBF-AML remains a favorable-risk group treated with intensive chemotherapy; targeted additions have not yet improved outcomes despite biologic rationale. Gemtuzumab ozogamicin (at reduced doses) remains an accepted component of some CBF-AML regimens. ELN and ESMO AML guidance continue to recommend cytarabine-based intensive chemotherapy for fit CBF-AML patients.