A Descriptive Analysis of Monoclonal Gammopathies in a Large Regional Healthcare System
Authors: Kaur Gagandeep , Brazel Danielle , Puglisi Leah , Hermel David Jacob 
Published: December 2024

Introduction
Monoclonal gammopathies comprise a heterogenous group of disorders arising from an abnormal B cell or plasma cell clone. All cases of multiple myeloma (MM), the second most prevalent hematological malignancy in the United States, are preceded by a monoclonal gammopathy, often identified in a precursor state known as monoclonal gammopathy of undetermined significance (MGUS). The annual risk of progression from MGUS to MM is about 1% with unclear precipitating factors. Recent data suggest that obesity may be associated with the transition from MGUS to MM, however this remains controversial due to inconsistent findings. Several reports have highlighted a potential link between Type 2 Diabetes (T2DM) and the development of MM. Moreover, some data suggest that metformin may be correlated with a decreased risk of progression in these patients. Here we provide a comprehensive analysis within a large regional institution focusing on co-exiting and progressive risk factors in patients with MGUS, with a detailed analysis of those who progress to smoldering myeloma (SMM) or MM.
Methods
We conducted a retrospective chart review of all patients diagnosed with MGUS or who had MGUS defining laboratory criteria within Scripps Health via the electronic medical record from January 2017 to April 2024. Demographic analyses included age, BMI, socioeconomic status, and tobacco use. Key risk factors examined included obesity, hypertension (HTN), T2DM, and hyperlipidemia (HLD). We also looked at rates of medication use for each of the previously listed comorbidities. Among the patients with monoclonal gammopathies, those with a diagnosis of MM or SMM during the time frame reviewed were analyzed independently. Those who developed other plasma cell dyscrasias or lymphoproliferative disorders were excluded.
Results
A cohort of 16,893 patients with a monoclonal gammopathy were identified with a median age of 75 years and a median BMI of 26.3. The majority of these patients were white (77.4%), followed by Asian (8.8%), other races (6.0%), and African American (4.5%). 27.5% of patients who had a monoclonal gammopathy had a bone marrow biopsy confirming MGUS. Of the entire cohort, 51 (0.3%) with a prior MGUS diagnosis progressed to smoldering myeloma (SMM) or MM after a median time to progression of 38 months. Within the cohort of MM and SMM, median age was 75 and median BMI 25.9. Comparing the MGUS and progression cohorts, respectively, there were similar rates of tobacco use (38.9% vs 47%), HTN (73.6% vs 72.5%), T2DM (34.8% vs 23.5%), and HLD (59.0% vs 51%). Among patients who progressed, there was a decreased prevalence of T2DM, though other co-morbidities were not significantly different. Notably the rate of non-insulin diabetic medication use was 23.8% and 11.8% within our monoclonal gammopathy and MM cohorts, respectively.
Conclusion
The findings suggest that metabolic and lifestyle factors such as HTN and HLD are prevalent in patients with disease progression, though are similar in those with MGUS who appear not to progress to MM and SMM in a limited time frame. To better understand the implications of gammopathies and clinical variables associated with progression, large multi-institutional, prolonged collaborations are needed.