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Light chain monoclonal gammopathy of undetermined significance is characterized by a high disappearance rate and low risk of progression on longitudinal analysis

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Abstract

We determined the 10-year progression rate of light chain monoclonal gammopathy of undetermined significance (LCMGUS) and investigated potential associations with cancer utilizing the German population-based Heinz Nixdorf Recall Study. The Heinz Nixdorf Recall Study comprises 4814 men and women aged 45–75 years. Serum samples from baseline (2000–2003) and five-year (2006–2008) and 10-year (2011–2015) follow-up examinations were screened for monoclonal free light chains (FLC). LCMGUS was defined as abnormal FLC ratio, increase of involved FLC with complete loss of immunoglobulin heavy chain, and absence of a history of lymphoproliferative disease (LPD). Seventy-five individuals with LCMGUS were identified across all three evaluation time points (median age 64 years; 43 (57%) male; FLCR > 1.65 65 (87%); FLCR ≤ 0.65 10 (13%)). After a median observation time of 11.5 years, none of the LCMGUS cases had progressed to overt LPD; in particular, we did not observe incident light chain multiple myeloma. On serial analysis 17/31 (55%), LCMGUS could not be confirmed and disappearance of the monoclonal protein was associated with low concentrations of the involved FLC. Individuals with LCMGUS had a 1.5-fold increased risk of cancer but did not show differences in overall survival or renal function as compared to individuals with normal FLC. In conclusion, LCMGUS represents a relatively benign condition with a high disappearance rate of the monoclonal protein on longitudinal analysis and normal overall survival at least in the population-based setting.

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Acknowledgements

We thank the participants of the Heinz Nixdorf Recall Study. We also thank the investigative group and the study personnel of the Heinz Nixdorf Recall Study.

Funding

This study was supported by an internal research grant to L.E. from the Faculty of Medicine of the University Hospital of Essen (IFORES). Parts of the study were funded by a research grant from Celgene, Munich, Germany. FREELITE test kits were provided by The Binding Site, Birmingham, UK, free of charge. The Heinz Nixdorf Recall study was supported by the Heinz Nixdorf Foundation [Chairman: Martin Nixdorf; Past Chairman: Dr Jur Gerhard Schmidt (deceased)], the Kulturstiftung Essen Germany, and by research grants from the German Research Council (DFG project ER 155/6-2, SI 236/8-1, SI 236/9-1) and the German Ministry of Education and Science (BMBF).

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Authors and Affiliations

  1. Institute of Medical Informatics, Biometry and Epidemiology, University Hospital Essen, Essen, Germany

    Benedikt W. Pelzer, Marina Arendt, Susanne Moebus, Lewin Eisele & Karl-Heinz Jöckel

  2. Department of Hematology, University Hospital Essen, Hufelandstr. 55, D-45122, Essen, Germany

    Benedikt W. Pelzer, Ulrich Dührsen & Jan Dürig

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  1. Benedikt W. Pelzer
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  2. Marina Arendt
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  3. Susanne Moebus
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  4. Lewin Eisele
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  5. Karl-Heinz Jöckel
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  6. Ulrich Dührsen
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Correspondence to Jan Dürig.

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Pelzer, B.W., Arendt, M., Moebus, S. et al. Light chain monoclonal gammopathy of undetermined significance is characterized by a high disappearance rate and low risk of progression on longitudinal analysis. Ann Hematol 97, 1463–1469 (2018). https://doi.org/10.1007/s00277-018-3305-x

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