Venetoclax-based combinations in high-risk myelodysplastic syndromes: highlights from ASH 2025 & EHA 2026

High-risk myelodysplastic syndromes (HR-MDS) are associated with poor survival despite standard therapy with hypomethylating agents (HMAs). Although the VERONA trial did not meet its primary endpoint, a granular interpretation of these results alongside real-life data may help identify patient subsets that could potentially benefit. At the 2025 American Society of Hematology (ASH) Meeting and at the 2026 European Hematology Association Congress (EHA), several studies reported updated data on venetoclax-based combinations in HR-MDS across clinical and biological subgroups. The randomized phase III VERONA study evaluated venetoclax plus azacitidine (VEN/HMA) versus azacitidine alone in the frontline setting, while additional phase I/II and real-life studies explored oral hypomethylating backbones, therapy-related disease, and molecularly defined subsets. Collectively, these data suggest that venetoclax enhances response rates in HR-MDS, although survival benefits remain heterogeneous, with a potential benefit observed when used as a bridge to transplantation. Given the lack of randomized data in transplant-eligible patients, this Correspondence provides a narrative, non-systematic review of the available evidence based mostly on abstracts and not peer reviewed publications. Additionally, we summarize the most clinically relevant findings and discuss their implications for future treatment strategies.