Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance

Abstract

Background: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older.

Methods: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder.

Results: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) - was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001).

Conclusions: Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.).

Figure 1. Rate of Progression of Monoclonal Gammopathy of Undetermined Significance (MGUS) per 100 Person-Years in the Entire Cohort

The primary end point of the study was progression to multiple myeloma or other plasma-cell or lymphoid disorders among patients with MGUS in a cohort of 1384 patients. Subgroups involving follow-up were analyzed with the use of a person-year approach, so patients may have been counted in both categories. Data on immunoglobulin type were excluded for 45 patients with biclonal status, data on the monoclonal protein (M protein) level were missing for 11, and data on the free light-chain ratio were missing for 236. The normal immunoglobulin type was IgG, with types other than IgG considered to be abnormal; the normal M protein level was less than 1.5 g per deciliter, with higher values considered to be abnormal.

Figure 2. Cumulative Incidence of Progression of MGUS, with Death Accounted for as a Competing Risk

I bars indicate 95% confidence intervals.

Figure 3. Observed Survival Rate in the Cohort versus the Expected Survival Rate in the Control Population

The numerical values are the observed rates of survival at 10, 20, 30, 35, and 40 years among the patients in the study and the expected rates in the age-and sex-matched control population.