Poor Prognosis for Subset of Patients With AML With Monocytic Differentiation Treated With Frontline Venetoclax and Hypomethylating Agents

According to a study from Cancer Medicine, among a subset of patients with newly diagnosed acute myeloid leukemia (AML) with a monocytic immunophenotype, a poor prognosis with treatment of venetoclax and hypomethylating agents was seen.

“Although the combination of venetoclax and hypomethylating agents results in impressive efficacy in AML, there is still a subset of patients who are refractory,” stated first study author Dian Jin, Zhejiang University School of Medicine, Hangzhou, China, and colleagues.

A total of 155 patients with newly diagnosed AML treated with frontline venetoclax and hypomethylating agents were enrolled in the trial. Monocyte-like AML was identified by flow cytometry with typical expression of monocytic markers, and M5—monocytic AML—was identified according to French, American, and British category.

Study results demonstrated 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 non-monocyte-like AML (CR/CRi rates, 26.7% vs 80%, P < 0.001; median PFS, 2.1 vs 8.8 months, P < 0.001; median OS, 9.2 vs 19 months, P = 0.013). Additionally, the 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.

 “Our study suggested that newly diagnosed monocyte‐like AML with high expression of CD4, CD14, CD64, and CD11b and low expression of CD117 had a poor response to frontline [venetoclax and hypomethylating agents] treatment,” concluded Dian Jin and colleagues.

 “When determining induction therapy for AML, we should carefully evaluate the expression of monocytic markers and their potential resistance to venetoclax‐based therapies, especially in adverse risk groups,” they added.

Source:

Jin D, He J, Chen H, et al. Impact of monocytic differentiation on acute myeloid leukemia patients treated with venetoclax and hypomethylating agents. Published online July 19, 2024. doi: 10.1002/cam4.7378