Treatment of TP53 -mutated myelodysplastic syndrome and acute myeloid leukemia with low-intensity metronomic decitabine and venetoclax.
Mendel Goldfinger, Ioannis Mantzaris, Aditi Shastri et al.
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In 30 seconds
This phase II clinical trial analysis examined low-intensity, once-weekly decitabine plus venetoclax in 40 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); 26 were treated in a prospective trial and 14 in a retrospective cohort. Overall response was 70% in AML and 57% in MDS. At a median follow-up of 12.9 months, median overall survival was 11.3 months for the full cohort. The authors reported a low toxicity profile, with no therapy-related fatalities and 7.5% 100-day mortality.
Key findings
- Overall response was 70% in AML and 57% in MDS.
- Median overall survival was 11.3 months overall, 11.6 months for AML, and 9.9 months for MDS.
- Among 31 patients with bi-allelic TP53 mutations, median overall survival was 10.4 months.
- Transfusion independence occurred in 58%; neutropenic fever occurred in 15%, with no therapy-related fatalities.
Why it matters
TP53-mutated myeloid malignancies have limited survival benefit with standard hypomethylating-agent and venetoclax dosing, which can also cause prolonged cytopenias. These results suggest that a metronomic schedule may achieve responses and transfusion independence with a reported low toxicity profile in this high-risk population. The findings provide a rationale for further evaluation but do not establish comparative benefit.
What to keep in mind
The analysis combined a prospective trial with a retrospective cohort and included only 40 patients. The abstract reports no comparator group, limiting conclusions about relative efficacy or safety.