Impact of MGUS on comorbidities and outcomes in patients with multiple myeloma: A propensity-matched analysis

Abstract Background: Multiple myeloma (MM) is a clonal plasma cell neoplasm projected to affect approximately 36,000 people and result in 12,000 deaths in the United States in 2025, according to the American Cancer Society. Monoclonal gammopathy of undetermined significance (MGUS) has a 1% rate of progression to MM. In this study we aimed to analyze effect of MGUS for osteoporosis, iron deficiency anemia, CKD, in hospital mortality rates and health care burdens between MGUS patients who progressed to MM and MM patients without history of MGUS. Methods: We conducted a propensity score matching analysis to assess the impact of MGUS on the development of osteoporosis among 148,045 patients diagnosed with multiple myeloma (MM) in the National Inpatient Sample (NIS) database from 2016 to 2022. A total of 5,035 MM patients had a documented history of MGUS. Propensity scores were estimated using covariates including age, gender, race, income quartile, length of stay, total hospital charges, and comorbidities. After matching, 988 MGUS patients were successfully matched to 988 non-MGUS controls. Logistic regression analysis was performed on the matched cohort to evaluate the association between MGUS and osteoporosis, chronic kidney disease (CKD), and iron deficiency anemia, adjusting for relevant clinical and demographic factors. Results: The mean age was similar between the MGUS and control groups (68.63 vs. 68.63 years). Females comprised 46.4% of the MGUS group and 46.5% of the control group. In multivariate analysis adjusting for potential confounders, MGUS was associated with 1.16-fold increased odds of osteoporosis; however, this was not statistically significant (p = 0.455). Prior to propensity matching, MGUS was associated with a significantly higher risk of osteoporosis (OR = 1.35, p = 0.026). Iron deficiency anemia was significantly more prevalent in the MGUS group (OR = 2.20, p < 0.001), and female patients were also more likely to have iron deficiency anemia (OR = 1.59, p = 0.015). Chronic kidney disease (CKD) was more frequently observed in the MGUS group (OR = 1.25, p = 0.028), and each additional year of age was associated with a 4% increased risk of CKD (OR = 1.04, p < 0.001). Female sex was associated with a lower risk of CKD (OR = 0.69, p < 0.001). While the MGUS group had higher mean total hospital charges (+$5,621) and longer length of stay (+0.43 days), these differences were not statistically significant (p = 0.625 and p = 0.904, respectively). In-hospital mortality was 29% lower in the MGUS group (OR = 0.71), but this difference also did not reach statistical significance (p = 0.118). Conclusion: In this large, matched cohort of multiple myeloma patients, a prior history of MGUS was not significantly associated with increased risk of osteoporosis or in-hospital mortality. However, MGUS was independently associated with higher odds of iron deficiency anemia and chronic kidney disease, suggesting a potential role of underlying plasma cell dysregulation in the development of these comorbidities.