High-risk myelodysplastic syndromes (HR-MDS) remain associated with poor survival despite standard treatment with hypomethylating agents (HMAs), and new data presented at the 2025 American Society of Hematology (ASH) Meeting and the 2026 European Hematology Association (EHA) Congress offer a nuanced picture of where venetoclax-based combinations may fit.
The centerpiece is the randomized phase III VERONA trial, which evaluated venetoclax plus azacitidine (VEN/HMA) against azacitidine alone in the frontline setting. Although VERONA did not meet its primary endpoint, the authors of a new Correspondence in Experimental Hematology & Oncology argue that a granular interpretation of the results, alongside real-life data, may help identify patient subsets that could potentially benefit from the combination.
Beyond VERONA, additional phase I/II and real-life studies reported updated findings on venetoclax-based combinations across clinical and biological subgroups. These explored oral hypomethylating backbones, therapy-related disease, and molecularly defined subsets of HR-MDS patients, reflecting a broad effort to define who gains most from adding the BCL-2 inhibitor to HMA therapy.
Collectively, the presented data suggest that venetoclax enhances response rates in HR-MDS. However, survival benefits appear heterogeneous across patient groups, meaning that improved responses do not uniformly translate into longer survival for everyone treated with these regimens.
One notable signal concerns transplantation. The available evidence points to a potential benefit when venetoclax-based combinations are used as a bridge to allogeneic transplantation, offering a possible role for the strategy in eligible patients awaiting this curative-intent procedure.
Importantly, the authors emphasize the limits of the current evidence base. There are no randomized data in transplant-eligible patients, and much of the reviewed material consists of conference abstracts rather than peer-reviewed publications. The Correspondence is therefore explicitly framed as a narrative, non-systematic review of the available evidence.
Within those constraints, the authors summarize the most clinically relevant findings from the meetings and discuss their implications for future treatment strategies in HR-MDS, a disease area where standard HMA therapy leaves many patients with poor outcomes.
The overall message for clinicians and researchers is twofold: venetoclax-based combinations can increase response rates in high-risk myelodysplastic syndromes, but survival gains remain inconsistent, and identifying which molecular, clinical, and disease-related subgroups truly benefit, particularly in the transplant setting, remains the key open question for future studies.
Subject of Research: Venetoclax-based combination therapy for high-risk myelodysplastic syndromes, including the VERONA trial and ASH 2025 and EHA 2026 updates
Article Title: Venetoclax-based combinations in high-risk myelodysplastic syndromes: highlights from ASH 2025 & EHA 2026
Article References: Zugasti, I., Cornejo, M., Castaño-Diez, S., Rodriguez-Sevilla, J. J., Cortes-Bullich, A., Esteve, J., & Diaz-Beya, M. (2026). Venetoclax-based combinations in high-risk myelodysplastic syndromes: highlights from ASH 2025 & EHA 2026. Experimental Hematology & Oncology, 15(1), Article 106. https://doi.org/10.1186/s40164-026-00832-x
Image Credits: AI Generated
DOI: 10.1186/s40164-026-00832-x
Keywords: high-risk myelodysplastic syndromes, venetoclax, azacitidine, hypomethylating agents, VERONA trial, ASH 2025, EHA 2026, bridge to transplantation, response rates, phase III trial, hematologic malignancies, Venetoclax-based
News Source: Nathaniel Bowman. (October 28, 2026). Venetoclax Combinations Show Promise in High-Risk MDS Despite Trial Setback. Scienmag.
