DP093 | HYPOMETHYLATING AGENTS ALONE OR IN COMBINATION WITH VENETOCLAX IN VERY ELDERLY ACUTE MYELOID LEUKEMIA PATIENTS: IS LESS BETTER THAN MORE?

Azacitidine/venetoclax combination is the standard of care for acute myeloid leukemia (AML) patients deemed unfit for intensive care programs, according to the VIALE-A trial results. Nevertheless, growing evidence unveils slightly different data from the aforementioned study. This multicenter, retrospective study investigates clinical outcomes of 182 elderly (≥75 years at diagnosis) AML patients treated between 2018 and 2023 with either hypomethylating agents (HMA) alone, azacitidine (n=84) or decitabine (n=21), or in combination with venetoclax (HMA/VEN; n=77). The primary objective was to compare treatment outcomes and tolerability in a real-world setting. Median age at diagnosis was significantly lower in the HMA/VEN group compared to HMA (76 vs 78 years; p = 0.001); a higher proportion of patients in the HMA/VEN subset had favorable performance status (ECOG-PS 0–2 in 96% vs 51% in the HMA group; p<0.001). Both cohorts had similar distribution in AML subtypes and ELN 2022 risk categories. Hospitalization during the first treatment cycle occurred more frequently in the HMA/VEN subset than in HMA (87% vs 72%; p=0.028), though median hospital stay was comparable (10 vs 11.5 days). Median outpatient visits per month (excluding those for therapy administration) were higher in the HMA/VEN group compared to HMA (4 vs 3; p<0.001). Despite this, the median number of treatment cycles was significantly lower in HMA/VEN patients than in HMA (4 vs 7; p=0.003), possibly due to early toxicity. Notably, the three-month early mortality rate was significantly higher in the HMA/VEN group (30% vs 16%; p=0.043) and the median OS favored the HMA group than HMA/VEN subset (12 months [range: 1–85] vs 8 months [1–53]; p=0.026). Composite response rates (complete remission + partial remission) were slightly higher in the HMA group than in HMA/VEN (61% vs 53%), though not statistically significant. In conclusion, our data from an unselected very elderly AML population show that the HMA/VEN combination treatment does not confer a survival advantage when compared to the HMA alone. Furthermore, the HMA/VEN therapy is more frequently associated with hospitalization and higher outpatient resource use. These findings underscore the need for individualized treatment strategies in these patients, for which prolonged OS and a good quality of life are the main clinical goals. Moreover, a careful patient selection is crucial when considering VEN-containing regimens in elderly AML patients.