Venetoclax and Azacitidine for the Treatment of Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Key claim: A phase I/II trial is evaluating the safety, optimal dosing, and efficacy of venetoclax combined with azacitidine in patients with relapsed or refractory high-risk MDS or CMML.
Abstract
This phase I/II trial investigates the side effects and best dose of venetoclax when given together with azacitidine and to see how well it works in treating patients with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine together may help to control myelodysplastic syndrome or chronic myelomonocytic leukemia.
Why this matters
Relapsed/refractory high-risk MDS and CMML have dismal outcomes with no standard salvage regimen, and prospective evidence in this post-HMA-failure setting is sparse. This trial extends the well-established frontline azacitidine + venetoclax doublet into the R/R space for both CMML and MDS/MPN overlap, helping define whether BCL-2 inhibition retains activity once HMA monotherapy has failed — a key gap distinct from the frontline AVENHIR and ASTX727+venetoclax efforts already in the CMML pipeline.