High-dose cytarabine with idarubicin consolidation for acute myeloid leukemia in first complete remission: a randomized controlled trial.

Whether adding anthracycline to intermediate- or high-dose cytarabine as consolidation is beneficial remains unclear in acute myeloid leukemia (AML). Eligible AML patients in first complete remission were randomly assigned (1:1) to receive either high-dose cytarabine with idarubicin (IA3 + 3) (idarubicin 10 mg/m, d1-3 and cytarabine 2 g/m, every 12 h, d1-3) or high-dose cytarabine (HDAC) (cytarabine 3 g/m, every 12 h, d1-3) regimens as first consolidation. The primary endpoint was the rate of negative measurable residual disease (MRD) after first consolidation. Between November 2018 and December 2021, 407 patients were assigned to IA3 + 3 (n = 204) or HDAC (n = 203) groups. MRD after first consolidation for IA3 + 3 and HDAC groups was 65.2% (95%CI: 58.6-71.8%) and 53.2% (46.3-60.1%) (P = 0.009). The 3-year cumulative incidence of relapse was 22.6% (95%CI :16.8-29.0%) and 34.0% (27.1-41.1%) (P = 0.014), DFS was 68.4% (61.5-75.3%) and 52.9% (45.4-60.5%) (P = 0.003), OS was 75.5% (69.0-82.1%) and 69.6% (62.4-76.7%) (P = 0.18) and treatment-related mortality was 8.8% (5.2-13.6%) and 13.0% (8.5-18.5%) (P = 0.23) in two groups, respectively. Eighty-seven (43%) and 114 (56%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), respectively (P = 0.006). IA3 + 3 regimen results in deeper remissions and reduces relapse compared to HDAC. This deeper remission improves DFS and translates into treatment advantage, with fewer patients undergoing allo-HSCT. (ClinicalTrials.gov, NCT03620955).