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ASCO 2026 | Myelodysplasia-related mutation dynamics and outcomes in patients with newly diagnosed AML
Naszrin Arani, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, provides insight into the findings of a retrospective analysis of myelodysplasia-related mutation dynamics and outcomes among patients with newly diagnosed acute myeloid leukemia (AML) treated with lower-intensity therapy. Dr Arani highlights that patients who cleared their myelodysplasia-related mutations at best response had superior overall survival (OS) and relapse-free survival (RFS), and suggests that these observations could help guide treatment decisions if validated prospectively. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
Mutations in ASXL1, EZH2, BCOR, STAG2, and mutations in the spliceosome complex are seen in people with AML with myelodysplasia-related features. And this is traditionally a group that faces adverse prognosis. We sought in our analysis to determine whether mutation dynamics in these myelodysplasia-related mutations can have any correlation with prognostic outcomes in people with newly diagnosed AML with myelodysplasia-related mutations...
Mutations in ASXL1, EZH2, BCOR, STAG2, and mutations in the spliceosome complex are seen in people with AML with myelodysplasia-related features. And this is traditionally a group that faces adverse prognosis. We sought in our analysis to determine whether mutation dynamics in these myelodysplasia-related mutations can have any correlation with prognostic outcomes in people with newly diagnosed AML with myelodysplasia-related mutations. So what we did was we retrospectively analyzed 185 patients who were treated with low-intensity therapy, especially with venetoclax at MD Anderson Cancer Center from 2017 to 2025, and looked at their myelodysplasia-related mutations at baseline and at best response.
And what we found was that in these people, 26% of patients were able to clear their myelodysplasia-related mutations, and 74% of them had persistent mutations at best response. And interestingly, in these people who cleared them, especially in people who had negative flow cytometry at best response, there was a superior overall survival and relapse-free survival in people who were myelodysplasia-related mutation negative. And again, especially in people who are flow cytometry negative. This did hold up in multivariate analysis. And people who had persistent myelodysplasia-related mutations actually had an inferior overall survival. They had a hazard ratio of 1.7. And the take-home message of this analysis is that dynamics of myelodysplasia-related mutations may provide prognostic information beyond the negative flow cytometry and could identify a high-risk population that might otherwise be missed with a negative flow cytometry result.
So based on these results, people who have persistent myelodysplasia-related mutations at best response and their inferior overall survival outcomes in this analysis one might infer that they have a greater likelihood to have a decreased overall survival and this could change your decision to go forward with like a transplant or your maintenance therapy duration or perhaps your strategy. But of course, some further analysis is needed to see whether this holds up prospectively.
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