Key Clinical Summary:

• Design/Population: A retrospective, community-based real-world analysis using a large EHR network evaluated outcomes with frontline venetoclax plus a hypomethylating agent (azacitidine or decitabine) in older adults with AML aged ≥ 70 years treated between 2015 and 2025.
• Key Outcomes: Median time to treatment discontinuation was just over 5 months, and median time to next treatment was 7.6 months, with no meaningful differences across older age subgroups, suggesting feasibility even in the very elderly. Median overall survival (OS) was 11 months, which was numerically shorter than VIALE-A but directionally comparable; 2-year OS was 27% and 48-month OS was 18%, indicating a subset achieving longer-term survival in routine practice.
• Clinical Relevance: Venetoclax-HMA induction was deliverable across advanced age groups with real-world survival approaching trial benchmarks, although early discontinuation was common, highlighting potential gaps in treatment optimization and supportive care. These findings support broader community adoption while underscoring the need for deeper chart-level analyses to refine real-world best practices.

Ira Zackon, MD, Ontada, Albany, New York, presented results from a large real-world analysis demonstrating that frontline venetoclax plus a hypomethylating agent was broadly deliverable to patients aged 70 years or older with acute myeloid leukemia (AML) at the 2025 ASH Annual Meeting & Exposition.

Median overall survival was 11 months, slightly lower than clinical trial data but encouragingly comparable, while outcomes were consistent across age subgroups. 

Dr Zackon concluded, “We need to do a deeper dive to describe this and get a more complete picture of contemporary AML treatment in the clinical setting.”

Transcript:

Hi, I am Dr Ira Zackon, a senior medical director with Ontada. We work in retrospective real-world data and research, and I'm happy here at ASH annual meeting to present some of our data in acute myeloid leukemia patients who are in the elderly population.

As we know, they provide a challenge to us. Yet there's been a movement away from intensive induction chemotherapy treatments to what we call non-intensive therapies, such as a hypomethylating agent, largely azacitidine or decitabine with venetoclax, a BCL2 inhibitor or sometimes a mutation driven targeted therapy. 

We wanted to look at what's happened at the community level. Our database is sourced in an electronic health record that reflects a large network of community practices, and we wanted to interrogate, since it was approved, the FDA approved venetoclax in combination with an HMA in October of 2020, or at least 2020, it had had accelerated approval as early as 2018.

Our study looked for AML patients who were 70 years or older and had received venetoclax-based therapy as their induction first-line therapy. This was in a larger time period of 2015 to 2025. We identified almost 1100 patients, 1093 patients who were treated with first line venetoclax-based therapy with an HMA.

What we saw was that first of all, our median age was 77 years old, so clearly an older population. It was fairly well distributed where about between the age of 70 and 80 was the majority, but a significant minority over 80 and over 85 to about 15% of the patients. Distributed over that age subgroups in the elderly population, 60% were male, which is not unusual and mostly a white population, 77%.

Then we looked at time to treatment discontinuation first. That's from the start of therapy. When was treatment discontinued, and that was just over 5 months. In this real-world setting, patients were discontinuing therapy somewhat early. We know that remissions can occur early, but they weren't necessarily sustaining the therapy, which you could continue until disease progression. That's 1 fact to note in the real-world setting. 

We also looked at time to next treatment (TTNT) where the median TTNT was 7.6 months. That means patients did get onto another treatment. Not all patients get onto another treatment. Again, when we looked at those 2 metrics, time to treatment discontinuation and time to next treatment, there was no difference across these age subgroups. It's at least telling us that this can be delivered even to the very elderly in an equivalent fashion, even if it may be less on therapy than it might have been in the trials.

Importantly, we looked at overall survival in this population, and our median overall survival was 11 months. When you look at the VIALE-A trial, which was the prospective clinical trial of azacitidine and venetoclax, the median overall survival was 14.7 months in some long-term follow up. Somewhat shorter in the real world. Again, it was also an older population and yet approximating it. Again, that's an encouraging survival signal. When we looked at the 24 month or 2-year survival, it was 27% in our population, VIALE-A was about 40%. Long-term at a 48-month overall survival, ours was 18% and it was about a little bit higher in VIALE-A so long-term, fairly equivalent outcomes in the long-term survival.

In conclusion of our study, to our knowledge, this is the largest retrospective community-based analysis at this time on these therapies. Encouraging that it can be delivered across these age groups, including the very elderly, and that the overall survival, although somewhat inferior to the clinical trials, which is not unusual, encouragingly close in some aspects.

We recognize in the community setting that there's a learning curve of delivering this therapy. There are some complexities or nuances to delivering in the dosing, dose reductions, drug interactions, end point management, that it does require some learning in order to treat these patients like this. That would only get better with experience.

I think the next steps are to do a more in-depth study of this patient population with chart abstraction. We were inquiring at a very high level on what's called structured data, data that is entered by the physicians into structured parts of the electronic health record that we can extract easily for analysis, but there's a rich unstructured data in the progress notes and other documents because we would want to know, okay, well what's the complete remission rate? What's that duration of remission? Even more prognostic profiles in terms of the cytogenetic profiles, as well as important events as to the mortality events. Transplantation events in this patient population will tend to be lower given the age of the population. 

We need to do a deeper dive to describe this and get a more complete picture of contemporary AML treatment in the clinical setting.

Source:

Zackon I, Engle H, Herms L, et al. Real-world analysis of treatment patterns and outcomes in older patients with Acute Myeloid Leukemia (AML) in the US community oncology setting. Dec 6-9, 2025; Orlando, FL. Abstract: 5190.

Pratz KW, Jonas BA, Vinod Pullarkat, et al. Long‐term follow‐up of VIALE‐A: Venetoclax and azacitidine in chemotherapy‐ineligible untreated acute myeloid leukemia. American Journal of Hematology. Published online February 11, 2024. doi:10.1002/ajh.27246