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However, little is known about the performance of venetoclax\u2010based regimens outside of clinical trials, given conflicting safety and efficacy data. Even less is known about the impact of the hypomethylating agent backbone. In this study, we demonstrate that decitabine\u2010venetoclax is associated with a significantly higher rate of grade three or higher thrombocytopenia, but lower rates of lymphocytopenia compared to azacitidine\u2010venetoclax. There was no difference in response or survival across ELN 2017 cytogenetic risk categories in the overall cohort. Significantly more patients succumb to relapsed or refractory disease than death from any other cause. We demonstrated that a Charlson comorbidity index score threshold of seven identifies exceptionally high\u2010risk patients, providing evidence for clinical use to reduce the risk of early treatment\u2010related mortality. Lastly, we provide evidence that measurable residual disease negativity and an <jats:italic>IDH<\/jats:italic> mutation predict a significant survival benefit outside clinical trials. Taken together, these data illuminate the real\u2010world performance of venetoclax and decitabine or azacitidine in the treatment of AML.<\/jats:p>","DOI":"10.1002\/jha2.663","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T11:56:24Z","timestamp":1677239784000},"page":"381-392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Venetoclax with decitabine or azacitidine in the first\u2010line treatment of acute myeloid leukemia"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4274-4249","authenticated-orcid":false,"given":"Ian M.","family":"Bouligny","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology Department of Internal Medicine Virginia Commonwealth University Massey Cancer Center  Richmond Virginia 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