Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia
Key claim: A phase Ib/II trial is evaluating axatilimab (anti-CSF-1R monoclonal antibody) alone or combined with azacitidine for safety and efficacy in advanced-phase MPN, MPN/MDS overlap, and high-risk CMML.
Abstract
This phase Ib/II trial tests the best dose of axatilimab and effectiveness of axatilimab with or without azacitidine for the treatment of patients with advanced phase myeloproliferative neoplasms (MPN), myeloproliferative neoplasm/myelodysplastic syndrome (MPN/MDS) overlap or high risk chronic myelomonocytic leukemia (CMML). Axatilimab is an antibody that is cloned from a single white blood cell that is known to be able to recognize cancer cells and block a protein on the surface of the white blood cells that may be involved in cancer cell growth. By blocking the proteins, this may slow or halt the growth of the cancer. Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving axatilimab with or without azacitidine may be safe and effective in treating patients with advanced phase MPN, MPN/MDS overlap or high risk CMML.
Why this matters
Axatilimab introduces CSF-1R blockade — a monocyte/macrophage trafficking axis previously unexplored in MPN — as a unifying therapeutic strategy across three subtypes (advanced MPN, MDS/MPN overlap, high-risk CMML) that share inflammatory/myelomonocytic biology but have historically been treated under distinct paradigms. For CMML, where monocytosis defines the disease, the mechanism is biologically rational; for transformed PMF and MDS/MPN overlap, the ± azacitidine design tests whether CSF-1R inhibition can augment HMA backbones. The trial expands the early-phase pipeline beyond JAK/HMA/BCL-2 combinations into stromal-immune microenvironment targeting.