Abstract Introduction: Monoclonal gammopathy refers to the presence of monoclonal immunoglobulins (M proteins) or free light chains (FLCs) produced by clonal plasma cells or B lymphocytes. It may precede multiple myeloma (MM), AL amyloidosis, or B-cell malignancies. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition defined by M protein 3 g/dL, 10% bone marrow plasma cells, and absence of end-organ damage. MGUS is subclassified into non-IgM, IgM, and light-chain subtypes, each with distinct progression risks. Overall risk of progression is ~0.5-1% per year. Prevalence increases with age and is higher in men and African American individuals. Real-world data on subtype prevalence and characteristics are limited, particularly in IgM MGUS. We conducted a single-institution retrospective study to characterize MGUS subtypes and evaluate demographic and laboratory differences, with a focus on IgM MGUS. Methods: MGUS cases diagnosed between 2019 and 2025 at UF Health Jacksonville under the care of a single hematology-oncology faculty member were retrospectively reviewed. Patients underwent a standardized workup including complete blood count, serum protein electrophoresis, immunofixation, quantitative immunoglobulins, serum FLCs, beta-2 microglobulin, lactate dehydrogenase (LDH), basic metabolic panel, and metastatic skeletal survey. The diagnosis date was based on initial abnormal labs. Patients were seen every 6 months. Patients aged ≥18 years were included; those with a prior or concurrent diagnosis of MM, Waldenström macroglobulinemia, or AL amyloidosis were excluded. Data collected included age, sex, race, and peak laboratory values at or near diagnosis: hemoglobin (Hb), white blood cell (WBC) count, absolute lymphocyte count (ALC), M-spike, immunoglobulin levels, kappa/lambda FLC ratio, beta-2 microglobulin, and LDH. MGUS subtypes were categorized by immunofixation. Descriptive statistics were performed in Google Sheets. Results: Forty-six patients were identified: IgG (n=27, 59%), IgM (n=14, 30%), and IgA (n=5, 11%). Mean age at diagnosis was 67 years for IgG, 66 for IgA, and 63.5 for IgM. Female predominance was observed in IgM (79%) and IgA (80%) groups, compared to 56% in IgG. Median follow-up was 2.1 years overall: 2.7 in IgG, 2.6 in IgA, and 1.8 in IgM. No progression to hematologic malignancy was observed during follow-up. Racial distribution varied by subtype. The IgG group was 75% African American, 21% white, and 4% Asian. IgM MGUS was 50% African American, 43% white, and 7% Native American. The IgA group included equal numbers of African American and white patients. Mean M-spike was highest in the IgG group (0.55 g/dL), followed by IgM and IgA (both 0.35). IgM MGUS had the highest peak IgM (2,453 mg/dL) and IgG (2,651) levels. IgA MGUS had the highest IgA level (850). Peak kappa FLC was highest in the IgG group (200.1 mg/L); peak lambda FLC was highest in the IgM group (301.7). The kappa/lambda FLC ratio was most skewed in the IgG group (26.33), compared to IgM (4.73) and IgA (2.58). Beta-2 microglobulin and LDH were also highest in the IgG group (6.9 mg/L and 433 U/L, respectively). Mean Hb was similar across groups (~12.9 g/dL in IgG and IgA; 12.7 in IgM). WBC and ALC were slightly higher in IgA (7.3 ×10³/µL; 1.7 ×10³/µL) and IgM (7.2; 2.3) than in IgG (6.2; 2.0). Conclusion: In this single-center cohort, IgG MGUS was most prevalent, consistent with prior studies. However, IgM MGUS accounted for 30% of cases - nearly double the 15% reported in population-based data. This may reflect regional or demographic factors and highlights the importance of localized research. The IgG group showed a strong predominance of African American patients, consistent with known MGUS epidemiology. In contrast, IgM MGUS exhibited a more balanced racial distribution and striking female predominance, which contrasts with earlier reports and may reflect biological or referral-related differences. Laboratory features differed by subtype. IgG MGUS showed higher M-spike values, markedly skewed FLC ratios, and elevated beta-2 microglobulin and LDH, suggestive of greater clonal activity. These findings emphasize the utility of real-world practice data in refining MGUS subtype characterization. Further multicenter studies are needed to validate these patterns and improve risk stratification across diverse patient populations.
Mikulas et al. (Mon,) studied this question.