Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine

Prognostic significance of monocytic-like phenotype in patients with AML treated with venetoclax and azacytidine

Abstract: The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (M...

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Main Authors: Lin-Pierre Zhao, Typhaine Dumas-Rivero, Lauren Barette, Lorea Aguinaga, Arij Cheffai, Clémentine Chauvel, Reinaldo Dal Bello, Emmanuel Raffoux, Emmanuelle Clappier, Matthieu Duchmann, Pierre Fenaux, Pierre Lemaire, Stephanie Mathis, Marie Sébert, Lionel Adès, Raphaël Itzykson
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Blood Advances
Online Access:http://www.sciencedirect.com/science/article/pii/S2473952925002332
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Summary:Abstract: The prognostic impact of monocytic differentiation in patients with acute myeloid leukemia (AML) receiving venetoclax (Ven) and azacitidine (Aza) remains unclear. In a prospective cohort of 86 newly diagnosed patients with AML treated with Ven-Aza, we used multiparametric flow cytometry (MFC) to define monoblasts as AML blasts coexpressing ≥2 monocytic markers (CD4, CD36, and CD64) per European LeukemiaNet (ELN) guidelines. Patients with higher monoblasts/CD45+ proportions had lower complete response rates (odds ratio, 0.24; P = .005) and significantly shorter overall survival (OS; 4.0 vs 14.9 months; P = .003). A ≥10% monoblasts/CD45+ threshold, identified via maximally selected rank statistics, stratified patients into monoblasthigh (≥10%) and monoblastlow (<10%) groups. MFC reclassified 20% of French-American-British (FAB) non-M4/5 and 15% of FAB M4/5 cases into monoblasthigh and monoblastlow groups, respectively. Multivariable analysis confirmed monoblasthigh status as an independent adverse prognostic factor for OS (hazard ratio [HR], 1.95; P = .023), with a particularly strong impact in ELN 2024 favorable-risk patients (HR, 2.81; P = .024). Our findings highlight monocytic differentiation, assessed via MFC, as a key predictor of Ven-Aza resistance and poor survival, independent of genetic classification. Given its availability in routine diagnostics, MFC-based monocytic assessment could improve AML risk stratification and treatment decisions in patients eligible for less intensive therapies. This trial was registered at www.clinicaltrials.gov as #NCT05326919.
ISSN:2473-9529

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