Venetoclax in Combination With ASTX727 for the Treatment of Chronic Myelomonocytic Leukemia and Other Myelodysplastic Syndrome/Myeloproliferative Neoplasm
Key claim: A phase II trial is evaluating whether oral decitabine/cedazuridine (ASTX727) combined with venetoclax is more effective than ASTX727 alone at reducing disease burden in patients with CMML or MDS/MPN with excess blasts.
Abstract
This phase II trial tests whether decitabine and cedazuridine (ASTX727) in combination with venetoclax work better than ASTX727 alone at decreasing symptoms of bone marrow cancer in patients with chronic myelomonocytic leukemia (CMML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) with excess blasts. Blasts are immature blood cells. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. The combination of ASTX727 and venetoclax may be more effective in reducing the cancer signs and symptoms in patients with CMML, or MDS/MPN with excess blasts.
Why this matters
HMA + venetoclax is the standard AML doublet but has been only partially validated in CMML (via AVENHIR with parenteral azacitidine) and remains largely untested in MDS/MPN overlap with excess blasts. Substituting oral ASTX727 for injectable azacitidine could meaningfully shift the practicality of this combination for chronic outpatient management in these overlap subtypes, where excess-blast disease has historically borrowed AML or MDS regimens without dedicated randomized evidence.