Daunorubicin-45 Vs. Daunorubicin-60 for Induction in Intermediate-Age Patients of AML: Results From a Randomized Trial.

Daunorubicin dose optimization remains crucial for AML treatment. While 90 mg/m2 benefits younger adults and 45 mg/m2 remains standard for older patients, the optimal dose for patients aged 55-65 years is unclear. We evaluated whether intermediate dose escalation to 60 mg/m2 would improve outcomes compared to that of standard 45 mg/m2 in this population. In this prospective, randomized, open-label, single-center trial, newly diagnosed AML patients aged 55-65 years were randomly assigned 1:1 to receive daunorubicin 45 mg/m2 (Group S) or 60 mg/m2 (Group M) on days 1-3, combined with cytarabine for the induction. At median follow-up of 35.9 months, no significant difference in OS was observed between the two groups (HR 1.24, 95% CI 0.80-1.91; p = 0.333). Median OS was 48.7 months (95% CI 28.2-NR) in Group S vs. 33.0 months (95% CI 22.2-71.6) in Group M. Five-year survival rates were comparable (45.2% vs. 39.8%). CR rates after first induction were equivalent (47.1% vs. 44.4%; RD +2.7%, 95% CI -17.4 to 12.0; p = 0.720). MRD-negative CR rates showed no difference (35.6% vs. 32.2%; p = 0.632). RFS (HR 1.38, 95% CI 0.84-2.26; p = 0.201) and EFS (HR 1.18, 95% CI 0.81-1.74; p = 0.389) were similar in both arms. Regarding safety, while overall infection rates were similar, Group M showed a significantly higher incidence of documented intestinal infections compared to Group S (22.5% vs. 8.0%; p = 0.011). Exploratory subgroup analyses revealed no consistent patterns favoring either strategy across clinical or molecular subgroups. Daunorubicin dose escalation from 45 to 60 mg/m2 provides no clinical benefit but significantly increases mucosal toxicity. Therefore, 45 mg/m2 should remain the preferred regimen for this population. Trial Registration: ClinicalTrials.gov identifier: NCT02432872.