A Phase II study testing an alternating low-intensity venetoclax-based regimen has shown high remission rates and durable survival in older or unfit patients with newly diagnosed acute myeloid leukemia.
The trial enrolled 190 patients with a median age of 68. 16% had favorable-risk disease by ELN 2022 criteria, 20% intermediate-risk, and 64% adverse-risk.
Overall, complete remission or CR with incomplete count recovery reached 84%. Among patients with TP53 wild-type AML, that rate hit 91%, with 77% achieving MRD-negative responses.
Median overall survival was 52 months, and median event-free survival 50 months. Two- and five-year OS rates were 60% and 45%, respectively. For those achieving MRD-negative CR, median OS was not yet reached, with a 2-year OS of 70%.
44% of responders went on to allogeneic stem cell transplant, suggesting the regimen can bridge to curative therapy.
The safety profile was manageable: 4-week mortality 1%, 8-week mortality 3%. Median neutrophil recovery took 27 days; platelet recovery 24 days. Most severe adverse events were infectious.
Researchers conclude this alternating venetoclax-based approach offers meaningful long-term benefit in a difficult-to-treat population.