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. 2010 May 15;375(9727):1721-8.
doi: 10.1016/S0140-6736(10)60482-5.

Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study

Angela Dispenzieri  1 , Jerry A Katzmann, Robert A Kyle, Dirk R Larson, L Joseph Melton 3rd, Colin L Colby, Terry M Therneau, Raynell Clark, Shaji K Kumar, Arthur Bradwell, Rafael Fonseca, D F Jelinek, S Vincent Rajkumar
Affiliations

Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study

Angela Dispenzieri et al. Lancet. .

Erratum in

  • Lancet. 2010 Jul 31;376(9738):332. doi: 10.1016/S0140-6736(10)61186-5

Abstract

Background: Monoclonal gammopathy of undetermined significance (MGUS) is defined by expression of heavy-chain immunoglobulin (IgH) and is the precursor lesion for 80% of cases of multiple myeloma. The remaining 20% are characterised by absence of IgH expression; we aimed to assess prevalence of a corresponding precursor entity, light-chain MGUS.

Methods: We used a population-based cohort, previously assembled to estimate MGUS prevalence, of 21,463 residents of Olmsted County, MN, USA, aged 50 years and older. We did a serum free light-chain assay on all samples with sufficient serum remaining, and immunofixation electrophoresis was done for all samples with an abnormal free light-chain ratio or abnormal protein electrophoresis results from the original study. Light-chain MGUS was defined as an abnormal free light-chain ratio with no IgH expression, plus increased concentration of the involved light chain. We calculated age-specific and sex-specific prevalence and rates of progression to lymphoproliferative disorders for light-chain and conventional MGUS and assessed incidence of renal disorders in patients with light-chain MGUS.

Findings: 610 (3.3%) of 18,357 people tested had an abnormal free light-chain ratio, of whom 213 had IgH expression that was diagnostic of conventional MGUS. 146 of the remaining 397 individuals had an increase of at least one free light chain and met criteria for light-chain MGUS. Prevalence of light-chain MGUS was 0.8% (95% CI 0.7-0.9), contributing to an overall MGUS prevalence of 4.2% (3.9-4.5). Risk of progression to multiple myeloma in patients with light-chain MGUS was 0.3% (0.1-0.8) per 100 person-years. 30 (23%) of 129 patients with light-chain MGUS were diagnosed with renal disease.

Interpretation: We define a clinical entity representing the light-chain equivalent of conventional MGUS and posing a risk of progression to light-chain multiple myeloma and related disorders.

Funding: US National Cancer Institute.

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Conflict of interest statement

CONFLICT OF INTEREST

No conflict of interest for J.A.K., D.R.L, D.R.L., C.L.C., L.J.M., T.M.T., R.C., S.K.K., R.F., D.F.J., or S.V.R. A.D. and R.A.K. have received honoraria from the Binding Site. A.B. is a director of The Binding Site, UK, which manufactures and sells the free light chain immunoassay kits.

Figures

Figure 1
Figure 1
Prevalence of MGUS, light chain MGUS (LC-MGUS), and abnormal free light chain ratio (FLC-R) without elevated free light chain among Olmsted County, Minnesota residents 50 years of age and older
Figure 2
Figure 2
Rates of progression to multiple myeloma and related disorders.
Figure 3
Figure 3
Definition of light chain MGUS (LC-MGUS) depends on free light chain ratio (FLC-R) cut-offs: normal reference range versus the renal reference range.
See this image and copyright information in PMC

Comment in

References

    1. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton LJ., 3rd Incidence of multiple myeloma in Olmsted County, Minnesota: Trend over 6 decades. Cancer. 2004;101(11):2667–74. - PubMed
    1. Kyle RA, Therneau TM, Rajkumar SV, et al. Prevalence of monoclonal gammopathy of undetermined significance. The New England journal of medicine. 2006;354(13):1362–9. - PubMed
    1. Bradwell AR, Carr-Smith HD, Mead GP, et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem. 2001;47(4):673–80. - PubMed
    1. Mead GP, Carr-Smith HD, Drayson MT, Bradwell AR. Detection of Bence Jones myeloma and monitoring of myeloma chemotherapy using immunoassays specific for free immunoglobulin light chains. Clin Lab. 2003;49(1–2):25–7. - PubMed
    1. Bradwell AR, Carr-Smith HD, Mead GP, Harvey TC, Drayson MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet. 2003;361(9356):489–91. - PubMed

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