Abstract 3651: Obesity, metabolic comorbidities, and lifestyle factors and their association with monoclonal gammopathies in a high-risk screened population: Results of the PROMISE study

Abstract Background: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition of multiple myeloma (MM) traditionally identified by serum protein electrophoresis (SPEP) and immunofixation (IFX). Recently, novel, ultra-sensitive mass spectrometry (MS)-based approaches have allowed for monoclonal (M)-protein detection at concentrations below SPEP levels. MGUS has only few known risk factors implicated in its development and progression. Thus, we analyze MS results of the PROMISE nationwide U.S. screening study to evaluate risk factors for (1) MGUS at traditional SPEP/IFX levels of detection and (2) low-level monoclonal gammopathies, which bear uncertain etiology and clinical significance. Methods: PROMISE enrolled individuals age ≥40 who are Black and/or have a first-degree relative with a blood cancer or MM precursor condition. Those with ≥2 first-degree relatives were eligible at age ≥18. Participants were screened for monoclonal gammopathy by MALDI-TOF MS and provided a survey querying metabolic comorbidities and lifestyle. M-protein concentrations ≥0.02 g/dL were considered traditionally-defined MGUS, whereas M-proteins <0.02 g/dL are hereafter referred to as monoclonal gammopathy of indeterminate potential (MGIP). Multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for exposure and MGUS/MGIP associations. Results: 1,893 screened participants completed the survey. MGUS and MGIP were detected in 13.4% and 22.0% of Blacks and 8.6% and 26.7% of individuals with family history. Adjusting for sex, age at screening, income, and education, obesity or BMI of ≥30 was associated with MGUS (OR, 1.55; 95% CI, 1.08-2.21), compared to BMI <30. Clinician-diagnosed hypertension (yes/no) and diabetes mellitus (yes/no) were associated with MGUS with ORs 1.44 (95% CI, 1.01-2.04) and 1.88 (95% CI, 1.004-3.51). There were no significant associations between MGUS and high cholesterol, high triglycerides, heart disease, myocardial infarction, or stroke. Short sleep of ≤6 hours/day was associated with MGUS (OR, 1.43; 95% CI, 1.01-2.03), compared to >6 hours/day. Physical activity (metabolic equivalents/week), smoking status (current, past, never), alcohol consumption (g/day) had no associations with MGUS. No risk factor associations were found for MGIP. Conclusion: In screening a high-risk population by mass spectrometry, we found associations of both traditionally established (obesity) and novel risk factors (diabetes, hypertension, short sleep) with MGUS. None of these exposures were associated with MGIP despite finding a high prevalence of MGIP in Blacks and individuals with family history, suggesting that these risk factors may not be etiologically involved in MGIP development but possibly its clonal expansion to more advanced stages. Citation Format: David J. Lee, Habib El-Khoury, Jean-Baptiste Alberge, D.J. Sakrikar, David Barnidge, Mark C. Perkins, Stephen Harding, Jacqueline Perry, Maya I. Davis, Julia Amstutz, Erica Horowitz, Timothy R. Rebbeck, Irene M. Ghobrial, Catherine R. Marinac. Obesity, metabolic comorbidities, and lifestyle factors and their association with monoclonal gammopathies in a high-risk screened population: Results of the PROMISE study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3651.