Impact of obesity and metabolic syndrome on survival in acute promyelocytic leukemia: A real-world analysis.

• DOI: 10.1200/jco.2025.43.16_suppl.e18526
• Publication Date: 2025-05-28T17:02:12Z
• Authors: Nolan Holley; Jonathan Shakesprere; Zainab Fatima; Kelly Griffith Ross; Lauren Westfall V...; Konstantinos Sdrimas; Bhavana Bhatnagar; Ashkan Emadi; Carl Shultz

e18526

Background: The prevalence of obesity and metabolic syndrome (MetS) continues to rise, necessitating a deeper understanding of their implications for cancer outcomes. Obesity is a recognized risk factor for acute promyelocytic leukemia (APL). Furthermore, higher body mass index has been linked to an increased risk of relapse and differentiation syndrome. Despite these findings, literature examining the relationship between obesity and long-term survival in APL remains limited. This study evaluates the association between obesity and 5-year overall survival (OS), with additional focus on the potential confounding or mediating role of MetS components. Methods: A retrospective cohort study was conducted using real-world data from the TriNetX global federated network. The primary outcome was 5-year OS in patients with APL, stratified by obesity status. A Cox proportional hazards model evaluated the association between obesity and 5-year OS. Univariable and multivariable models were used to adjust for potential confounders, including sex, age, hypertension, hyperlipidemia, hypertriglyceridemia, and type 2 diabetes mellitus (T2DM). Inclusion of these covariates targeted the potential influence of components of MetS on outcomes. Results: A total of 8,420 patients with obesity and 17,782 patients without obesity were included. Obesity conferred a 27.9% reduction in 5-year mortality risk in univariable analysis (HR=0.757, p <0.001) and a 15.5% reduction in multivariable analysis (HR=0.857, p <0.001). Among covariates, male sex (HR=1.208, p <0.001) and age (HR=1.034, p <0.001) were associated with worse 5-year OS. In contrast, T2DM (HR=0.917, p =0.003) and hyperlipidemia (HR=0.915, p =0.001) were independently associated with improved 5-year OS. Neither hypertension (HR=1.007, p =0.764) nor hypertriglyceridemia (HR=0.974, p =0.745) demonstrated a significant relationship with 5-year OS. Conclusions: This study shows that obesity, a known APL risk factor, was paradoxically associated with improved 5-year OS in univariable and multivariable analyses. Additionally, T2DM and hyperlipidemia, components of MetS, were linked to survival benefit. These findings suggest that while obesity and MetS contribute to APL development, they may also modulate disease biology or treatment response to improve survival. Although database studies have limitations, they offer valuable insights for generating hypotheses. We plan to further validate these findings using internal APL datasets from our institution.

5-Year OS

HR 95% CI

p

Univariable Analysis

Obesity 0.757 (0.724, 0.791) <0.001

Multivariable Analysis

Obesity 0.857 (0.819, 0.896) <0.001

Male 1.208 (1.16, 1.257) <0.001

Age 1.034 (1.032, 1.035) <0.001

Hypertension 1.007 (0.96, 1.057) 0.764

T2DM 0.917 (0.866, 0.97) 0.003

Hypertriglyceridemia 0.974 (0.829, 1.143) 0.7451

Hyperlipidemia 0.915 (0.866, 0.966) 0.001