Impact of obesity on survival outcomes in Acute Myeloid Leukemia patients treated with hypomethylating agents: A retrospective multicenter cohort study using real-world data

Abstract Background Obesity is a growing global health concern and has been associated with worse outcomes in various malignancies. However, its impact on survival in acute myeloid leukemia (AML), particularly in patients treated with hypomethylating agents (HMAs), remains poorly defined. Given the increasing use of HMAs in older or unfit AML patients, understanding the influence of obesity on treatment outcomes is critical for risk stratification and therapy optimization Methods This retrospective cohort study utilized the TriNetX Analytics Network to identify adult patients diagnosed with acute myeloid leukemia (AML) between January 2015 and December 2023. Eligible patients were identified using ICD-10-CM codes corresponding to AML subtypes, excluding acute promyelocytic leukemia (APL). Patients were required to have received treatment with a hypomethylating agent—either azacitidine or decitabine—as initial therapy. Propensity score matching was employed to balance cohorts based on demographic characteristics including age, sex, race, and ethnicity. Survival outcomes were compared between patients with obesity (BMI ≥ 30) and those with BMI < 30, with subgroup analyses stratified by obesity class (Class I: BMI 30–34.9, Class II: 35–39.9, Class III: ≥ 40). Kaplan-Meier analysis and Cox proportional hazards models were used to estimate overall survival and assess hazard ratios. Result After matching, each cohort included 1,491 patients, achieving balance across key demographics including age (mean 67.2 ± 11.8 vs. 67.3 ± 12.1 years), sex (54.13% male vs. 53.59% male), ethnicity (80.62% vs. 81.49% non-Hispanic), and White race (81.29% vs. 81.89%). Median overall survival (OS) was significantly shorter in the BMI ≥ 30 group (276 days) compared to the BMI < 30 group (319 days), with survival probabilities at the end of the time window of 45.10% and 46.76%, respectively. The hazard ratio (HR) for mortality in the BMI ≥ 30 group was 1.168 (95% CI: 1.051–1.297, p < 0.0001), indicating a significantly higher risk of death. In subgroup analyses by obesity class, Class I (BMI 30–34.9) had a median OS of 302 days vs. 330 days (HR 1.157, 95% CI: 1.008–1.327, p = 0.0374), Class II (BMI 35–39.9) had a median OS of 209 vs. 303 days (HR 1.343, 95% CI: 1.097–1.644, p = 0.0002), and Class III (BMI ≥ 40) had a median OS of 217 days vs. 265 days, with a survival probability of 42.02% and HR of 1.419 (95% CI: 1.105–1.821, p = 0.0019), demonstrating a clear, obesity class-dependent increase in mortality risk among AML patients treated with hypomethylating agents. Conclusion Obesity is independently associated with inferior overall survival in AML patients treated with hypomethylating agents, with progressively worse outcomes across higher obesity classes. These findings highlight the prognostic relevance of BMI in AML and suggest that obesity may contribute to therapeutic resistance or increased treatment-related toxicity. Further prospective studies are warranted to explore underlying mechanisms and to guide personalized treatment approaches in this population.