DP027 | CLINICAL SIGNIFICANCE OF MEASURABLE RESIDUAL DISEASE STATUS IN REAL WORLD ACUTE MYELOID LEUKEMIA PATIENTS RECEIVING HYPOMETHYLATING AGENTS PLUS VENETOCLAX

Hypomethylating agents (HMAs) combined with venetoclax (VEN) are considered the standard of care for patients (pts) with acute myeloid leukemia (AML) unfit to intensive chemotherapy. However, the prognostic value of measurable residual disease (MRD) in pts receiving this combination in the real-world setting remains uncertain. Our study investigated the impact of MRD status on overall survival (OS) in a real-world group of AML patients treated with HMAs-VEN. The analysis included 37 pts treated at the Onco-Hematology Department of Fondazione Policlinico Tor Vergata with HMAs-VEN combination between 2018 and 2025. Median age at diagnosis was 73 (range 50-82). According to ELN2017, 4/37 (11%), 22/37 (60%), and 9/37 (24%) were classified as favourable, intermediate, and adverse risk, respectively. Risk classification was not attributable in the remaining 2 (5%) cases. IDH1/2 was the most commonly detected molecular aberration, harboured by 30% of the pts. NPM1 and FLT3 (ITD or TKD) mutations were present in 22% and 19% of the pts, respectively. Response assessment was conducted after cycle 1 and every 3 cycles thereafter. Thirty-two pts were evaluable for response, whereas 5 were excluded due to early death. Composite complete remission (CRc) was achieved in 23/32 (71.8%) pts; in 4/23 (17%), 7/23 (30%) and 8/23 (35%) after cycle 1, 2 and 4, respectively. MRD assessment was available for all 23 pts in CRc, either through multiparameter flow cytometry (19/23, 82.6%) or polymerase chain reaction for NPM1-positive cases (4/23, 17.4%). MRD negativity rate was 10% after cycle 1 and 43% at the time of best response. Median number of cycles to MRD negativity was 3 (range 1-9). The median OS of the entire cohort was 11.1 months; pts achieving CRc had superior median OS than those not responding (17.4 vs 5.5 months, respectively, p=0.002). Considering survival since the achievement of best response, we observed a trend toward a better 1-year OS among MRD negative cases as compared to MRD positive ones (median OS NR vs 9.9 months, respectively) (Fig. 1). In conclusion, we observed that most of CRc are obtained within the first two cycles of therapy and that achievement of MRD negativity improves outcomes, even when occurring at later timepoints.