Annals of Hematology

, Volume 97, Issue 8, pp 1463–1469 | Cite as

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

  • Benedikt W. Pelzer
  • Marina Arendt
  • Susanne Moebus
  • Lewin Eisele
  • Karl-Heinz Jöckel
  • Ulrich Dührsen
  • Jan Dürig
  • on behalf of the Heinz Nixdorf Recall Study Investigative Group
Original Article


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.


Light chain MGUS Germany Population-based Cancer Renal disease 



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 information

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

277_2018_3305_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 26 kb)


  1. 1.
    Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, Therneau TM, Clark R, Kumar SK, Bradwell A, Fonseca R, Jelinek DF, Rajkumar SV (2010) Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet 375(9727):1721–1728. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Eisele L, Durig J, Huttmann A, Duhrsen U, Assert R, Bokhof B, Erbel R, Mann K, Jockel KH, Moebus S, Heinz Nixdorf Recall Study Investigative G (2012) Prevalence and progression of monoclonal gammopathy of undetermined significance and light-chain MGUS in Germany. Ann Hematol 91(2):243–248. CrossRefPubMedGoogle Scholar
  3. 3.
    Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, Melton LJ 3rd (2002) A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 346(8):564–569. CrossRefPubMedGoogle Scholar
  4. 4.
    Schmermund A, Mohlenkamp S, Stang A, Gronemeyer D, Seibel R, Hirche H, Mann K, Siffert W, Lauterbach K, Siegrist J, Jockel KH, Erbel R (2002) Assessment of clinically silent atherosclerotic disease and established and novel risk factors for predicting myocardial infarction and cardiac death in healthy middle-aged subjects: rationale and design of the Heinz Nixdorf RECALL Study. Risk Factors, Evaluation of Coronary Calcium and Lifestyle. Am Heart J 144(2):212–218CrossRefPubMedGoogle Scholar
  5. 5.
    Stang A, Moebus S, Dragano N, Beck EM, Mohlenkamp S, Schmermund A, Siegrist J, Erbel R, Jockel KH, Heinz Nixdorf Recall Study Investigation G (2005) Baseline recruitment and analyses of nonresponse of the Heinz Nixdorf Recall Study: identifiability of phone numbers as the major determinant of response. Eur J Epidemiol 20(6):489–496CrossRefPubMedGoogle Scholar
  6. 6.
    Katzmann JA, Clark RJ, Abraham RS, Bryant S, Lymp JF, Bradwell AR, Kyle RA (2002) Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 48(9):1437–1444PubMedGoogle Scholar
  7. 7.
    Hill PG, Forsyth JM, Rai B, Mayne S (2006) Serum free light chains: an alternative to the urine Bence Jones proteins screening test for monoclonal gammopathies. Clin Chem 52(9):1743–1748. CrossRefPubMedGoogle Scholar
  8. 8.
    Hutchison CA, Basnayake K, Cockwell P (2009) Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol 5(11):621–628. CrossRefPubMedGoogle Scholar
  9. 9.
    Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, Van Lente F, Chronic Kidney Disease Epidemiology C (2007) Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53(4):766–772. CrossRefPubMedGoogle Scholar
  10. 10.
    Kuhnemund A, Liebisch P, Bauchmuller K, zur Hausen A, Veelken H, Wasch R, Engelhardt M (2009) ‘Light-chain escape-multiple myeloma’—an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring. J Cancer Res Clin Oncol 135(3):477–484. CrossRefPubMedGoogle Scholar
  11. 11.
    Cesana C, Klersy C, Barbarano L, Nosari AM, Crugnola M, Pungolino E, Gargantini L, Granata S, Valentini M, Morra E (2002) Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol 20(6):1625–1634. CrossRefPubMedGoogle Scholar
  12. 12.
    Kyle RA, Therneau TM, Rajkumar SV, Remstein ED, Offord JR, Larson DR, Plevak MF, Melton LJ 3rd (2003) Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 102(10):3759–3764. CrossRefPubMedGoogle Scholar
  13. 13.
    Murray DL, Seningen JL, Dispenzieri A, Snyder MR, Kyle RA, Rajkumar SV, Katzmann JA (2012) Laboratory persistence and clinical progression of small monoclonal abnormalities. Am J Clin Pathol 138(4):609–613. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Gregersen H, Mellemkjaer L, Salling Ibsen J, Sorensen HT, Olsen JH, Pedersen JO, Dahlerup JF (2000) Cancer risk in patients with monoclonal gammopathy of undetermined significance. Am J Hematol 63(1):1–6CrossRefPubMedGoogle Scholar
  15. 15.
    Colls BM, Lorier MA (1975) Immunocytoma, cancer and other associations of monoclonal gammopathy: a review of 224 cases. N Z Med J 82(549):221–226PubMedGoogle Scholar
  16. 16.
    Solomon A (1977) Homogeneous (monoclonal) immunoglobulins in cancer. Am J Med 63(2):169–176CrossRefPubMedGoogle Scholar
  17. 17.
    Maurer MJ, Cerhan JR, Katzmann JA, Link BK, Allmer C, Zent CS, Call TG, Rabe KG, Hanson CA, Kay NE, Slager SL, Witzig TE, Shanafelt TD (2011) Monoclonal and polyclonal serum free light chains and clinical outcome in chronic lymphocytic leukemia. Blood 118(10):2821–2826. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Maurer MJ, Micallef IN, Cerhan JR, Katzmann JA, Link BK, Colgan JP, Habermann TM, Inwards DJ, Markovic SN, Ansell SM, Porrata LF, Johnston PB, Nowakowski GS, Thompson CA, Gupta M, Syrbu SI, Kurtin PJ, Macon WR, Nikcevich DA, Witzig TE (2011) Elevated serum free light chains are associated with event-free and overall survival in two independent cohorts of patients with diffuse large B-cell lymphoma. J Clin Oncol 29(12):1620–1626. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Witzig TE, Maurer MJ, Habermann TM, Link BK, Micallef IN, Nowakowski GS, Ansell SM, Colgan JP, Inwards DJ, Porrata LF, Markovic SN, Johnston PB, Lin Y, Thompson C, Gupta M, Katzmann JA, Cerhan JR (2014) Elevated monoclonal and polyclonal serum immunoglobulin free light chain as prognostic factors in B- and T-cell non-Hodgkin lymphoma. Am J Hematol 89(12):1116–1120. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Witzig TE, Maurer MJ, Stenson MJ, Allmer C, Macon W, Link B, Katzmann JA, Gupta M (2014) Elevated serum monoclonal and polyclonal free light chains and interferon inducible protein-10 predicts inferior prognosis in untreated diffuse large B-cell lymphoma. Am J Hematol 89(4):417–422. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Benedikt W. Pelzer
    • 1
    • 2
  • Marina Arendt
    • 1
  • Susanne Moebus
    • 1
  • Lewin Eisele
    • 1
  • Karl-Heinz Jöckel
    • 1
  • Ulrich Dührsen
    • 2
  • Jan Dürig
    • 2
  • on behalf of the Heinz Nixdorf Recall Study Investigative Group
  1. 1.Institute of Medical Informatics, Biometry and EpidemiologyUniversity Hospital EssenEssenGermany
  2. 2.Department of HematologyUniversity Hospital EssenEssenGermany

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