Prognostic impact of measurable residual disease in AML patients treated frontline with azacitidine and venetoclax: results from the French VENAURA registry.

Measurable residual disease (MRD) is a key prognostic marker in acute myeloid leukemia (AML), but its significance in patients treated with azacitidine and venetoclax (AZA/VEN) outside clinical trials remains unclear. We retrospectively analyzed 220 newly diagnosed AML patients from the French VENAURA registry who achieved composite complete remission and underwent MRD evaluation by multiparametric flow cytometry (MFC, LAIP/LSC) and/or NPM1 RT-qPCR. Cumulative MRD negativity was achieved in 62-67% of patients. Attaining MRD negativity at any time was strongly associated with superior overall survival (OS: 31.3 months vs 15.7 months (HR = 0.47) for LAIP, not reached vs 10.8 months (HR = 0.38) for NPM1; all p < 0.001) and lower cumulative incidence of relapse. Dual LAIP/LSC negativity (NEG/NEG) conferred the best outcomes compared to NEG/POS (HR = 0.36, p = 0.02), POS/NEG (HR = 0.24, p < 0.001) and POS/POS (HR = 0.26, p = 0.26) status. Importantly, MRD response mitigated the adverse prognostic impact of ELN 2024 intermediate/poor risk, with MRD-negative patients achieving outcomes comparable to favorable-risk cases. MRD kinetics (early vs late responders) did not affect survival, while G-CSF use improved MRD conversion and OS. In real-world AZA/VEN-treated AML, achieving deep MRD negativity, by MFC or NPM1 RT-qPCR, emerges as the dominant prognostic determinant, overriding baseline risk and supporting its integration into response-adapted strategies.