Mortality in Patients with Monoclonal Gammopathy of Undetermined Significance: an Analysis of National Health and Nutrition Examination Survey

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder with an annual risk of ~1% of progression to more advanced diseases, including multiple myeloma (MM). Few studies reported mortality risk in patients with MGUS, among which the diagnosis of MGUS was typically incidental due to unrelated symptoms or laboratory abnormalities. This study aims to compare the survival of MGUS patients with the U.S. general population using a nationally representative screening-based survey. Methods: Data were obtained from the third National Health and Nutrition Examination Survey (NHANES III) 1988-1994 and continuous NHANES 1999-2004, with follow-up all-cause mortality data through December 31, 2019. Participants were screened for MGUS by protein electrophoresis, immunofixation, and kappa and lambda free light chain assays in serum. Multivariable Cox-proportional regressions were performed, adjusting for demographic characteristics (age, gender, race/ethnicity, education, income, body mass index [BMI]), health behaviors (smoking, physical activity), baseline medical conditions (hypertension, diabetes, osteoporosis, myocardial infarction, stroke, congestive heart failure, coronary heart disease, peripheral vascular disease [PVD], arthritis, liver diseases, chronic obstructive pulmonary disease, renal diseases, cancer), and survey year. We also tested the interaction between race/ethnicity and MGUS diagnosis in the fully adjusted model. The NHANES complex sampling design was accounted for in all analyses to obtain population estimates. Results: The prevalence of MGUS among the U.S. population aged 50 years or older was 2.5% in 1988-1994 (sample size n=6,557; population size N=56,136,480) and 2.3% in 1999-2004 (n=5,847; N=68,835,295). MGUS patients were older and more likely to have PVD (13.1% vs. 7.7%, p = 0.03). No evidence was found showing a difference in gender distribution, education, income, BMI, and other comorbidities between the two populations. In NHANES 1999-2004, MGUS was associated with an increased risk of death (Hazard ratios [HR] 1.20, 95% CI: 1.02-1.41, p = 0.03) compared to the general population. NHANES III also showed a trend toward increased risk of mortality (HR 1.15, 95% CI: 0.89-1.48, p = 0.27). No interaction between race/ethnicity and MGUS diagnosis was found. It was notable that PVD was associated with an increased risk of death (HR 1.67, 95% CI: 1.43-1.94, p < 0.001). Conclusion: In the large cohort of NHANES participants, MGUS was associated with an increased risk of mortality. MGUS is typically viewed as a “benign” condition that has the potential to progress to cancer. These findings suggest that there may be alternate health implications to a diagnosis of MGUS. Future studies should focus on the causes of death in this population and the role of MGUS. Citation Format: Mengmeng Ji, John Huber, Mei Wang, Yi-Hsuan Shih, Yao-Chi Yu, Lawrence Liu, Theodore Thomas, Martin W. Schoen, Kristen M. Sanfilippo, Graham A. Colditz, Shi-Yi Wang, Su-Hsin Chang. Mortality in patients with monoclonal gammopathy of undetermined significance: an analysis of National Health and Nutrition Examination Survey [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6480.