Prevalence of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Light-Chain MGUS (LCMGUS) In a Metropolitan Area In Germany

We utilized the biobank of the ongoing population-based, prospective Heinz Nixdorf Recall Study to determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) and a recently defined entity – light-chain MGUS (LCMGUS) – in the densely populated Ruhr area in Germany.

The Heinz Nixdorf Recall study cohort comprises 4814 men and women from 3 large adjacent cities in Germany. Subjects were randomly selected from statutory lists of residence and gave informed consent. We screened serum samples from the baseline examination which took place from 2000 until 2003. Standard serum electrophoresis (SPE) was combined with parallel screening immunofixation electrophoresis (scIFE) using pentavalent antisera (Hydragel 12 IF, Penta-Kit, Sebia, Fulda, Germany). Where a monoclonal band was visible or suspected, confirmatory IFE followed. Free light-chain (FLC) κ and λ measurements were performed on a Dade Behring BNII automated nephelometer (Siemens, Germany) utilizing a commercially available kit (FREELITE, The Binding Site Ltd, Birmingham, UK). Definition of MGUS cases was based on common criteria including monoclonal protein concentration, laboratory results, and disease history. LCMGUS cases were defined as an abnormal FLC ratio, an increase in the FLC that caused the abnormal ratio and no detectable intact immunoglobulin (Dispenzieri et al. Lancet 2010: 1721-8). Age-standardization of prevalences was performed by direct standardization to the U.S. population 2000.

165 MGUS cases were identified in a total of 4708 screened samples, translating into a prevalence of 3.5% (95% CI, 3.0 – 4.1). The median age of MGUS cases was 63 years (range 47 – 75), 103 (62%) were of male gender, and prevalence increased with age. The age-standardized prevalence was 3.9% (95% CI 3.2 – 4.5) which was significantly higher (p<0.05) than previously reported (Kyle et al. NEJM 2006: 1362-9). Immunoglobulin isotypes were IgG 59%, IgA 17%, IgM 28%, biclonal 2.4%, kappa 55%, and lambda 44%. Concentrations of monoclonal proteins ranged from unmeasurable – 22.4 g/l with a median of 5.3 g/l. After a median observational time of 5 years, 3 MGUS cases had progressed to multiple myeloma and 1 case developed a diffuse large B-cell lymphoma, representing a progression rate of 0.5%/year (95% CI 0.13 – 1.3). An abnormal FLC ratio was detected in 222 samples. SPE + scIFE showed an intact immunoglobulin in 39 of these samples, thus representing conventional MGUS. A total of 34 (19%) of the 183 individuals with abnormal FLC ratios and no intact immunoglobulin had an increase in concentration of the FLC causing the abnormal ratio and thus met LCMGUS criteria. The overall prevalence of LCMGUS was 0.7% (95% CI 0.5 – 1.0) and the age-standardized prevalence was 0.8 (95% CI 0.5 – 1.1). None of the LCMGUS cases progressed during the observational period.

The higher MGUS prevalence of 3.9% in the Heinz Nixdorf Recall cohort compared to previous reports can be explained by the combined SPE + scIFE screening approach. Re-evaluation of the gels without the pentavalent tracks resulted in a prevalence similar to that reported for Olmsted County, Minnesota, U.S. The prevalence of the recently defined entity LCMGUS in the Heinz Nixdorf Recall cohort also compares favourably with the recently reported prevalence. Further characterization of MGUS and LCMGUS cases in the well-defined Heinz Nixdorf Recall cohort is the focus of ongoing analyzes.

Eisele:Celgene: Research Funding. Dürig:Celgene: Research Funding.