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More than 25 therapeutic agents are currently being evaluated in phase 1 or phase 2 clinical trials for CMML and other myeloid malignancies, often in combination with a HMA backbone. Several novel agents, such as sotatercept, ruxolitinib, lenzilumab, and tagraxofusp have shown promising clinical efficacy in CMML. Current evidence supports the idea that effective treatment in CMML will likely require combination therapy targeting multiple pathways, which emphasizes the need for additional new therapeutic options. This review focuses on