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Acute myeloid leukemia (AML) predominantly affects elderly population. This poses challenges in management, as patients are frequently not candidates for intensive therapy given comorbidities or frailty. Currently, azacitidine (AZA), either as monotherapy or in combination regimens, is the backbone treatment in this group of patients. We review the mechanism of action, pharmacology, clinical efficacy, and safety of AZA. It reviews current combination therapies of AZA with other targeted therapies for the treatment of newly diagnosed AML. AZA is a cornerstone for the treatment of patients considered ineligible for intensive chemotherapy induction, but better results and therapies are required for these patients. AZA has shown synergistic properties when combined with other medications. Its safety profile and few drug interactions make it a suitable medication to use as backbone. Newer therapies are being combined with AZA, demonstrating safety and in cases, improved responses, and survival. AZA/venetoclax has emerged as the standard of care for patients who are ineligible for intensive chemotherapy. Doublet and triplet combinations are increasingly being studied. With the results observed in elderly patients, the intensive chemotherapy paradigm might be put to test in younger populations, with AZA combinations being at the forefront.

Azacitidine and its role in the upfront treatment of acute myeloid leukemia