Impact of monocytic differentiation on acute myeloid leukemia patients treated with venetoclax and hypomethylating agents

Abstract Introduction Although the combination of venetoclax (VEN) and hypomethylating agents (HMAs) results in impressive efficacy in acute myeloid leukemia (AML), there is still a subset of patients who are refractory. We investigated the outcomes of AML patients with monocytic differentiation who were treated with frontline VEN/HMA. Methods A total of 155 patients with newly diagnosed AML treated with frontline VEN/HMA were enrolled in the study. Monocyte‐like AML was identified by flow cytometry with typical expression of monocytic markers, and M5 was identified according to French, American, and British category. We compared the outcomes of patients with different characteristics. Results The rate of complete remission (CR) and CR with incomplete recovery of blood counts (CRi), progression‐free survival (PFS), and overall survival (OS) in monocyte‐like AML were inferior to those in nonmonocyte‐like AML (CR/CRi rates, 26.7% vs. 80.0%, p < 0.001; median PFS, 2.1 vs. 8.8 months, p < 0.001; median OS, 9.2 vs. 19 months, p = 0.013). CR/CRi rate in M5 was lower than that in non‐M5 (60.7% vs. 75.5%, p = 0.049). Multivariate analyses showed that monocyte‐like AML was associated with lower odds of CR/CRi and higher risk of progression. Conclusion Our study suggested that newly diagnosed AML with a monocytic immunophenotype had a poor prognosis with VEN/HMA treatment.