Demographic and laboratory features of monoclonal gammopathy of undetermined significance (MGUS) subtypes in a single-center cohort Free

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.