Emerging Data Suggest Select Benefit for Venetoclax in MDS: Ivo Carre, PhD

The VERONA (NCT04401748) trial evaluating venetoclax with azacitidine in high-risk myelodysplastic syndromes (MDS) fell short of its primary goal, showing no significant advantage over azacitidine alone and prompting safety concerns in the first-line setting, explains Ivo Carre, PhD, a senior business analyst at Lifescience Dynamics. But new subgroup analyses presented at the American Society of Hematology (ASH) 2025 meeting may reveal a more complex picture.

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Transcript

With ASH expected to present new data on high-risk MDS, what are the most promising findings regarding the efficacy of venetoclax plus azacitidine?

The venetoclax plus azacitidine trial, which came from AbbVie and was titled VERONA, was actually quite an interesting one. So it failed, unfortunately, earlier this year, and we saw the initial data earlier; I believe it was in June at SOHO [Society of Hematologic Oncology] 2025. It basically showed that a ven-aza arm had no sort of significant difference to just azacitidine alone in high-risk MDS patients. In itself, that is not great, given the fact that venetoclax comes with additional sorts of safety and tolerability issues, and the debate around whether or not it is still going to be useful or even pertinent to use venetoclax plus aza in the first-line treatment is now sort of the main debate.

But what we're seeing at ASH this year is a bit more sort of subgroup data, where they've sort of divided out the sort of population to stratify based on age firstly and then also blast counts. And it's in these patients that are younger than 75 and in patients with blast counts above 5% where, while not significant, there is a trend towards improved efficacy. And then on the alternative side, what they're also showing is that the trial was strangely sort of powered towards having high rates of deleterious mutations, TP53 being the main one, which may have skewed some of the initial data. When they do hazard ratio analysis, they show that in TP53 patients, specifically as well, there is no trend occurring towards increased efficacy. We sort of got this balance between there potentially being some effect in patients with more favorable sorts of mutations as well as sort of younger ages, but then perhaps excluding those deleterious mutations, there may be benefits as well.