Background: phase III RCT included 657 17-60 y/o patients with untreated AML. Favorable risk 13.6%, 41.1% intermediate, 26.6% indeterminate, and 18.7% unfavorable.

Arm A: cytarabine 100 mg x7d infusion + daunorubicin 90 mg/mg/m2 daily x3
Arm B: cytarabine 100 mg x7d infusion + daunorubicin 45 mg/mg/m2 daily x3

BMBx on d12-14. Patients with CR received either alloHSCT or Gemtuzumab ozogamycin f/b autoHSCT.

Primary end point: OS
mFollow up: 25.2m

mOS for all patients: 23.7m vs 15.7m, arm A vs arm B respectively; HR multivariate 0.72, 95% CI, 0.58 to 0.89; P=.002
mOS for Favorable risk group did not reach.
mOS for intermediate group: 32.3m vs 17.8m, arm A vs arm B respectively; HR 0.67; P=.02.
mOS for unfavorable group: <11m for both groups without significant difference, HR 0.85, P=.45
Complete remission: 70.6% vs 57.3%, received consolidation: 57:8% vs 53.6%

Main adverse events. Grade 3-5 in arm A vs arm B respectively: cardiac tox 7.9% vs 7.2; reduced LVEF 1.3% vs 0; death rates during induction 5.5% vs 4.5, P=0.60.

Conclusions: high-dose daunorubicin significantly improves CR and OS in patients with favorable and intermediate risk and patients <50 y/o.

Study update: Patients with DNMT3A and NPM1, between 50-60 y/o with mutations in FLT-3 ITD or NPM1 also benefitted from high-dose Daunorubicin.

Summarized by Veli Bakalov, MD

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