The Role of CPX-351 in the Acute Myeloid Leukemia Treatment Landscape: Mechanism of Action, Efficacy, and Safety

CPX-351 (also known as VYXEOS® or Vyxeos liposomal) is a dual-drug liposomal encapsulation of cytarabine and daunorubicin in a synergistic 5:1 molar ratio and was the first example that utilized CombiPlex®, a combination drug technology platform. Superior efficacy with CPX-351 in the pivotal phase 3 randomized clinical trial versus its conventional free-drug counterpart led to its approval for the treatment of newly diagnosed therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes in multiple countries. Emerging evidence indicates that CPX-351 affords additional benefits compared with conventional chemotherapy, including protection against intestinal dysbiosis and fungal colonization, fewer infectious complications, and a lower incidence of cardiotoxicity. This review examines the mechanisms underlying CPX-351’s therapeutic effects and highlights its expanding role in AML treatment by summarizing efficacy and safety data from preclinical models, the pivotal clinical trial, and real-world studies. Particular focus is given to recent findings on CPX-351’s intestinal and cardioprotective properties, which together strengthen its safety and efficacy profile compared with conventional chemotherapy.