A phase 1 trial shows that a venetoclax-based transplant regimen is safe and effective for high-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia patients. The study focused on older patients with poor-risk features, including TP53 mutations, using a reduced-intensity conditioning of venetoclax with fludarabine and busulfan, followed by post-transplant maintenance with venetoclax and oral decitabine/cedazuridine.
Results were encouraging: two-year overall survival was 67%, progression-free survival was 53%, and there were no treatment-related deaths. Most patients successfully moved into the maintenance phase, which began around day 55 post-transplant. While blood cell counts were affected, severe graft-versus-host disease was rare, showing the regimen is well-tolerated even in a vulnerable population.
Researchers highlight that using venetoclax both before and after transplant could offer a new strategy for poor-risk patients who often cannot receive intensive chemotherapy. They also recommend monitoring minimal residual disease with next-generation sequencing to identify which patients are most likely to benefit from this approach.