High-Dose Cytarabine with Idarubicin Versus High-Dose Cytarabine within First Consolidation for Acute Myeloid Leukemia in First Complete Remission: An Open-Label, Multicenter, Randomized, Phase 3 Trial

Backgrounds：

Whether adding anthracycline to intermediate- or high-dose cytarabine as consolidation is beneficial remains unclear in acute myeloid leukemia (AML). We investigated the efficacy and safety of high-dose cytarabine with idarubicin as consolidation for AML in first complete remission (CR1).

Methods:

We performed the open-label, randomized phase 3 trial at 16 hospitals in China. Eligible AML patients in CR1 were randomly assigned (1:1) to receive either high-dose cytarabine with idarubicin (IA3+3) (idarubicin 10mg/m², d1-3 and cytarabine 2g/m², q12h, d1-3) or high-dose cytarabine (HDAC) (cytarabine 3g/m², q12h, d1-3) regimens as first consolidation. The primary endpoint was the rate of measurable residual disease negativity (MRD^-) after first consolidation. Secondary endpoints included cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS), treatment-related mortality (TRM) and adverse events (AEs).

Results

Between November 2018 and December 2021, a total of 407 eligible patients were enrolled and randomly assigned to IA3+3(n=204) or HDAC(n=203) groups. The MRD^- rates for IA3+3 and HDAC groups were 65.2% (95%CI: 58.6%-71.8%) and 53.2% (46.3%-60.1%) (RR=1.23, 95%CI:1.04-1.44, P =0.01). Median follow-up time was 37.3 months, the 3-year CIR, DFS, OS and TRM were 22.6% (95%CI :16.8%-29.0%) and 34.0% (27.1%-41.1%) (P=0.01), 68.4% (95%CI :61.5%-75.3%) and 52.9% (45.4%-60.5%) (P=0.003), 75.5% (95% CI :69.0%-82.1%) and 69.6% (62.4%-76.7%) (P=0.18), 8.8% (95%CI :5.2%-13.6%) and 13.0% (8.5%-18.5%) (P=0.23) in two groups, respectively. Ultimately, the patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) were 87 and 114 cases, respectively (P=0.006). Within 28 days after first consolidation, the most common grade 3 or higher AEs were thrombocytopenia (196[96%]vs 196[97%]), neutropenia (195[96%] vs 185[91%]), anemia (165[81%] vs 152[75%]), febrile neutropenia (146[72%] vs 128[63%]) and infections (104[51%] vs 83[41%]). One patient died from infection in IA3+3 group.

Conclusions

IA3+3 resulted in deeper remissions, reduced relapse and was well-tolerated compared to HDAC. This deeper remission improved DFS and translated into treatment advantage, with fewer patients undergoing allo-HSCT. This regimen may be an appropriate consolidation option for AML in CR1.

No relevant conflicts of interest to declare.