Abstract
Background/Objectives: Minimal residual disease (MRD) negativity is associated with improved outcomes in acute myeloid leukemia (AML) patients. In this retrospective observational real-life case series study, we investigated the efficacy and safety of venetoclax dose adjustment in unfit AML patients and the role of WT1 expression levels as a surrogate marker of MRD monitoring. Methods: A total of 24 consecutive unfit AML patients treated with azacytidine and venetoclax were enrolled in this study, and MRD monitoring was performed by flow cytometry as per international guidelines and by WT1 expression levels assessed by RT-qPCR. Dose adjustment of venetoclax was decided based on MRD status and the onset of grade > 2 neutropenia. Results: The overall response rate was 87.5%, and 16 patients achieved a response already at the first re-evaluation (66.7%). No statistically significant differences were observed between patients who received the standard dose and those with venetoclax dose adjustment in terms of overall survival (19.6 months vs. 30.1 months, respectively; p = 0.9428) and progression-free survival (not reached vs. 22.1 months, respectively; p = 0.3865), although a numerical trend toward lower relapse rates was observed in subjects with late (33.3%) or early and late dose reduction (37.5%) compared to those who had dose adjustment only at the first re-evaluation (75%) (p = 0.3014). The toxicity rate was 33.3% in patients who had early and late dose adjustments, which was lower than that observed with early adjustment (58.3%) and than that reported in the VIALE-A study (84%). Conclusions: Reduced-dose venetoclax regimens (from 28 to 21 days per cycle) in unfit AML patients do not affect response rates or survival and are associated with comparable rates of neutropenia and infectious events, supporting flexible dosing strategies based on patient response and side effects. In addition, WT1 expression could serve as a reliable marker for MRD monitoring.