BACKGROUND: We conducted a randomized controlled trial to compare intermediate doses (IDAC) with high doses of cytarabine (HDAC) as postinduction therapy in patients 18 to 60 years of age with newly diagnosed acute myeloid leukemia (AML). The main objectives were to evaluate noninferiority in overall survival (OS) after IDAC and safety.

METHODS: Patients 18 to 60 years of age with newly diagnosed AML, except those with core-binding factor, acute promyelocytic, Philadelphia chromosome-positive, or post-myeloproliferative neoplasm AML, were eligible. After the induction course, we randomly assigned patients to either IDAC (1500 mg/m²/12 hours) or HDAC (3000 mg/m²/12 hours). Patients with intermediate- and adverse-risk AML were eligible for allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. The primary end point was OS in a predefined per-protocol analysis population. The primary analyses were performed in 1132 randomly assigned patients, with a noninferiority outcome adjusted on the European Leukemia Net (ELN) 2022 risk group, the use of induction anthracycline, the response to induction, and HSCT as a function of time following treatment.

RESULTS: At 5 years, OS was estimated at 59.3% (95% confidence interval [CI], 55.0 to 63.3) in the IDAC group versus 57.5% (95% CI, 53.3 to 61.5) in the HDAC group (adjusted hazard ratio, 0.96; 95% CI, 0.80 to 1.15; noninferiority test, P=0.0042). A preplanned analysis was unable to detect any interaction between IDAC or HDAC treatment effect and patient subgroups, including those defined by the ELN 2022 risk group or response to induction prior to random assignment. In addition, the severity of chemotherapy-induced myelosuppression and the incidence of related adverse events were lower after IDAC.

CONCLUSIONS: Our trial shows noninferior outcomes in patients 18 to 60 years of age with newly diagnosed AML treated with low- versus high-dose cytarabine; this occurred with similar or lower toxicities. (Funded by the Regional Clinical Research Office, Angers and others; EudraCT number, 2014-000699-24; ClinicalTrials.gov number, NCT02416388.).