Monoclonal Gammopathy of Undertermined Significance (MGUS): Clinical Predictors of Malignant Transformation in 434 Patients with a Long Follow-Up from a Single Institution.

Background: MGUS is a common disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenström’s macroglobulinemia (WM) or primary amyloidosis (AL). Although about one fourth of these individuals will evolve into a malignant disease with a transformation rate of 1% per year, there are not well-established predictors of outcome.

Aim: To identify predictor features of malignant transformation in a large series of patients with MGUS and prolonged follow-up.

Patients and methods: Four hundred and thirty-four patients (200 M/234 F; median age 66 years) diagnosed with MGUS in a single institution from September 1970 to January 2001 with a minimum follow-up of one year were included in the study. All patients had an M-protein size < 30g/L. Bone marrow aspirates were reviewed independently by two of the authors and the proportion of bone marrow plasma cells (BMPC) were estimated from a 500 cell-count by each observer. The median follow-up was 5.2 years (range: 1–28.8 years) with 84 patients followed for more than 10 years.

Results: The type of M-protein was IgG in 67.2% of the cases, IgA in 18.8%, IgM in 11.9%, light chain in 1% and biclonal in 1%. The light chain was kappa type in 56.4% of the patients. The median M-protein size was 15.6 g/L (<10 g/L in 10.8%, 10–20 g/L in 61.7%, and > 20g/L in 27.4%). The median percentage of BMPC in 305 reviewed samples was 4.6% (range: 0.4–25). After a median follow-up of 5.2 years, 50 patients (11.5%) have evolved into a malignant monoclonal gammopathy (44 MM, 5 WM and 1 AL). The median time to progression was 5.4 yrs (range: 1.4 – 16.9). The risk of transformation was 15.4% (95% CI: 10.5–20.3) and 34% (95% CI 22.6–45.3) and 34% (95% CI: 22.6–45.3) at 10 and 20 years, respectively. The variables associated with a higher risk of transformation were IgA-type (p=0.003), kappa light chain (p=0.009), the amount of M-protein (<15 vs >15 g/L, p=0.005) and the percentage of BMPC (<5% vs >5%, p=0.007).

Conclusions: In this series of patients with MGUS, the type (i.e. IgA or kappa) and size of M-protein (>15g/L) as well as the percentage of bone marrow plasma cells (>5%) significantly predicted malignance transformation.