Adding venetoclax or hypomethylating agents to induction chemotherapy as first-line treatment for adults with acute myeloid leukemia: a retrospective case-cohort study

Background:The response rate of traditional first-line induction chemotherapy (IC) for newly diagnosed acute myeloid leukemia needs to be improved, but it is not clear whether adding venetoclax or hypomethylating agents (HMAs) to IC will improve the response rate.Objective:To determine whether venetoclax or HMAs could increase the response rate of IC in patients with newly diagnosed acute myeloid leukemia (AML).Design:A retrospective, propensity score matching analysis.Methods:Newly diagnosed AML patients at Tongji Hospital between 2021 and 2023 were included in this study. By matching cases and controls based on age, gender, baseline bone marrow blast cell proportion, type of AML, and the National Comprehensive Cancer Network (NCCN) risk stratification group, we compared the response rate (CR, CR/CRi, ORR, and MRD negative) and hematological adverse events in newly diagnosed AML treated with IC plus venetoclax or HMAs versus IC alone after one cycle of IC.Results:The addition of venetoclax could improve CR/CRi of IC (83.8% for IC plus venetoclax vs 66.1% for IC alone, p = 0.029). The addition of venetoclax to IA regimen did not improve CR/CRi of IA regimen (76.9% for IA plus venetoclax vs 76.2% for IA alone, p = 0.986). The addition of HMAs could not only improves CR/CRi of IC (85.3%% for IC plus HMAs vs 65.4% for IC alone, p = 0.002) but also improves CR/CRi of IA regimen (91.3% for IA plus HMAs vs 70.0% for IA alone, p = 0.034). The addition of HMAs could improve CR/CRi of patients with adverse mutations (FLT3, IDH1/2, K/NRAS) after IC. The addition of venetoclax and HMAs both extended the duration of agranulocytosis and thrombocytopenia.Conclusion:Adding HMAs might improve CR/CRi of IC including IA. Adding venetoclax might not improve CR/CRi of IA. A well-designed prospective randomized controlled study is now warranted.