Monoclonal Gammopathy of Undetermined Significance (MGUS): Predictors of Outcome and Recognition of an Evolving Type.

MGUS occurs in up to 3% of persons older than 50 years and the probability of malignant evolution is 1% per year. The risk of progression from MGUS to a symptomatic monoclonal gammopathy has been investigated in a number of series. However, only the presenting features have been considered while the evolutive pattern during the first years of follow-up has not been taken into account. The aim of our study was to investigate the predictors of outcome considering both the initial features and the pattern of evolution of the M-protein size during the first three years in a large series of patients with MGUS with long follow-up. Three-hundred and fifty nine patients (160 M, 199 F; median age 66 yrs) diagnosed with MGUS at a single institution were included in the study. Patients who showed an inequivocal increase in their M-protein size at the serum electrophoresis during the first three years of follow-up were considered as evolving while the remainders were considered as non-evolving. In the overall series the median values for serum M-protein level and for the proportion of bone marrow plasma cells (BMPC) were 14.8 g/L and 4%, respectively. Three hundred an thirty patients had a non-evolving MGUS while 29 fulfilled the criteria for the evolving type. The M-protein size and the proportion of BMPC at diagnosis were similar in both types of MGUS. The IgG type was more frequent in the non-evolving (65% vs. 45%, p=0.005) whereas the IgA and IgM type were more frequent in the evolving type (55% vs. 32%, p=0.04). Overall, 32 patients developed malignant transformation after a median follow-up of 93 months. Fourteen of the 29 (48%) evolving patients developed symptomatic multiple myeloma while only 18 out of the 330 (5%) remaining patients with non-evolving MGUS progressed to a malignant condition. The progression rate at 10 and 20 years of follow-up for the evolving and the non-evolving types was 55% vs. 10% and 80% vs. 13%, respectively. No patient in the non-evolving type evolved to a malignant condition after the first 12 years of follow-up. The predictors for malignant transformation at the univariate analysis were: the type of MGUS (evolving vs. non-evolving, p<0.001), a proportion of BMPC higher than 5% (p=0.001), the immunoglobulin isotype (IgA vs. IgG, p=0.007) and the M-protein size greater than 15 g/L (p=0.05). At the multivariate analysis the features significantly associated to a higher risk of progression were: the evolving type (RR 12.1, p<0.001,), the IgA type (RR 2.9, p=0.006) and the M-protein concentration (RR 2.2, p=0.044).

Conclusions: The evolutive pattern of the serum M-protein during the first years of follow-up is the most important risk factor for progression in patients with MGUS.