Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2–3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1–2% per year for the next 10 years. Testing should be done 2–3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4–6 months for 1 year and, if stable, every 6–12 months.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003; 121: 749–757.

    Article  Google Scholar 

  2. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 2006; 354: 1362–1369.

    Article  CAS  PubMed  Google Scholar 

  3. Cohen HJ, Crawford J, Rao MK, Pieper CF, Currie MS . Racial differences in the prevalence of monoclonal gammopathy in a community-based sample of the elderly.[erratum appears in Am J Med 1998 Oct;105(4):362]. Am J Med 1998; 104: 439–444.

    Article  CAS  PubMed  Google Scholar 

  4. Singh J, Dudley Jr AW, Kulig KA . Increased incidence of monoclonal gammopathy of undetermined significance in blacks and its age-related differences with whites on the basis of a study of 397 men and one woman in a hospital setting. J Lab Clin Med 1990; 116: 785–789.

    CAS  PubMed  Google Scholar 

  5. Landgren O, Katzmann JA, Hsing AW, Pfeiffer RM, Kyle RA, Yeboah ED et al. Prevalence of monoclonal gammopathy of undetermined significance among men in Ghana. Mayo Clin Proc 2007; 82: 1468–1473.

    Article  PubMed  Google Scholar 

  6. Iwanaga M, Tagawa M, Tsukasaki K, Kamihira S, Tomonaga M . Prevalence of monoclonal gammopathy of undetermined significance: study of 52,802 persons in Nagasaki City, Japan. Mayo Clin Proc 2007; 82: 1474–1479.

    Article  PubMed  Google Scholar 

  7. Landgren O, Kristinsson SY, Goldin LR, Caporaso NE, Blimark C, Mellqvist UH et al. Risk of plasma-cell and lymphoproliferative disorders among 14,621 first-degree relatives of 4,458 patients with monoclonal gammopathy of undetermined significance (MGUS) in Sweden. BLOOD 2009; 114: 791–795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Vachon CM, Kyle RA, Therneau TM, Foreman BJ, Larson DR, Colby CL et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood 2009; 114: 785–790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kyle RA, Therneau TM, Melton III LJ, Dispenzieri A, Larson D, Benson J et al. Monoclonal gammopathy of undetermined significance: estimated incidence and duration prior to recognition. Blood (Abstract) 2007; 110: 79a.

    Google Scholar 

  10. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Melton III LJ . Long-term follow-up of 241 patients with monoclonal gammopathy of undetermined significance: the original Mayo Clinic series 25 years later.[see comment]. Mayo Clinic Proc 2004; 79: 859–866.

    Article  Google Scholar 

  11. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. [see comment]. New Engl J Med 2002; 346: 564–569.

    Article  PubMed  Google Scholar 

  12. Rosinol L, Cibeira MT, Montoto S, Rozman M, Esteve J, Filella X et al. Monoclonal gammopathy of undetermined significance: predictors of malignant transformation and recognition of an evolving type characterized by a progressive increase in M protein size. Mayo Clin Proc 2007; 82: 428–434.

    Article  CAS  PubMed  Google Scholar 

  13. Blade J, Lopez-Guillermo A, Rozman C, Cervantes F, Salgado C, Aguilar JL et al. Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance. Br J Haematol 1992; 81: 391–394.

    Article  CAS  PubMed  Google Scholar 

  14. Cesana C, Klersy C, Barbarano L, Nosari AM, Crugnola M, Pungolino E et al. Prognostic factors for malignant transformation in monoclonal gammopathy of undetermined significance and smoldering multiple myeloma. J Clin Oncol 2002; 20: 1625–1634.

    Article  PubMed  Google Scholar 

  15. Baldini L, Guffanti A, Cesana BM, Colombi M, Chiorboli O, Damilano I et al. Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy. Blood 1996; 87: 912–918.

    CAS  PubMed  Google Scholar 

  16. Rajkumar SV, Kyle RA, Therneau TM, Melton III LJ, Bradwell AR, Clark RJ et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 2005; 106: 812–817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Perez-Persona E, Vidriales MB, Mateo G, Garcia-Sanz R, Mateos MV, de Coca AG et al. New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells. Blood 2007; 110: 2586–2592.

    Article  CAS  PubMed  Google Scholar 

  18. Nowakowski GS, Witzig TE, Dingli D, Tracz MJ, Gertz MA, Lacy MQ et al. Circulating plasma cells detected by flow cytometry as a predictor of survival in 302 patients with newly diagnosed multiple myeloma. Blood 2005; 106: 2276–2279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Anderson KC, Kyle RA, Rajkumar SV, Stewart AK, Weber D, Richardson P . Clinically relevant end points and new drug approvals for myeloma. Leukemia 2008; 22: 231–239.

    Article  CAS  PubMed  Google Scholar 

  20. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med 2007; 356: 2582–2590.

    Article  CAS  PubMed  Google Scholar 

  21. Dispenzieri A, Kyle RA, Katzmann JA, Therneau TM, Larson D, Benson J et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008; 111: 785–789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Dimopoulos MA, Moulopoulos LA, Maniatis A, Alexanian R . Solitary plasmacytoma of bone and asymptomatic multiple myeloma. Blood 2000; 96: 2037–2044.

    CAS  PubMed  Google Scholar 

  23. Wang M, Alexanian R, Delasalle K, Weber D . Abnormal MRI of spine is the dominant risk factor for early progression of asymptomatic multiple myeloma. Blood 2003; 102: 687a (abstract).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to R A Kyle.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Appendix

Appendix

International Myeloma Working Group

Rafat Abonour, Indiana University School of Medicine, Indianapolis, Indiana, USA

Ray Alexanian, MD Anderson, Houston, Texas, USA

Kenneth C Anderson, DFCI, Boston, Massachusetts, USA

Michael Attal, Purpan Hospital, Toulouse, France

Herve Avet-Loiseau, Institute de Biologie, Nantes, France

Ashraf Badros, University of Maryland, Baltimore, Maryland, USA

Bart Barlogie, MIRT UAMS Little Rock, Arkanas, USA

Dalsu Baris, National Cancer Institute, Bethesda, Maryland, USA

Regis Batille, Institute de Biologie, Nantes, France

Meral Beksac, Ankara University, Ankara, Turkey

Andrew Belch, Cross Cancer Institute, Alberta, Canada

Bill Bensinger, Fred Hutchinson Cancer Center, Seattle, Washington, USA

P Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, Arizona, USA

Jenny Bird, Bristol Haematology and Oncology Center, Bristol, UK

Joan Bladé, Hospital Clinica, Barcelona, Spain

Mario Boccadoro, University of Torino, Torino, Italy

Michele Cavo, Universita di Bologna, Bologna, Italy

Asher Chanan-Khan, Roswell Park Cancer Institute, Buffalo, New York, USA

Wen Ming Chen, MM Research Center of Beijing, Beijing, China

Tony Child, Leeds General Hospital, Leeds, United Kingdom

James Chim, Department of Medicine, Queen Mary Hospital, Hong Kong

Wee-Joo Chng, National University Health System, Singapore

Ray Comenzo, Tufts Medical School, Boston, Massachusetts, USA

John Crowley, Cancer Research and Biostatistics, Seattle, Washington, USA

William Dalton, H Lee Moffitt, Tampa, Florida, USA

Faith Davies, Royal Marsden Hospital, London, England

Cármino de Souza, Univeridade de Campinas, Caminas, Brazil

Michel Delforge, University Hospital Gasthuisberg, Leuven, Belgium

Meletios Dimopoulos, University of Athens School of Medicine, Athens, Greece

Angela Dispenzieri, Mayo Clinic, Rochester, Minnesota, USA

Brian GM Durie, Cedars-Sinai Outpatient Cancer Center, Los Angeles, California, USA

Johannes Drach, University of Vienna, Vienna, Austria

Hermann Einsele, Universitätsklinik Würzburg, Würzburg, Germany

Theirry Facon, Centre Hospitalier Regional Universitaire de Lille, Lille, France

Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos Aires, Argentina

Jean-Paul Fermand, Hopitaux de Paris, Paris, France

Rafael Fonseca, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Gösta Gahrton, Karolinska Institute for Medicine, Huddinge, Sweden

Ramon Garcia-Sanz, University Hospital of Salamanca, Salamanca, Spain

Christina Gasparetto, Duke University Medical Center, Durham, North Carolina, USA

Morie Gertz, Mayo Clinic, Rochester, Minnesota, USA

John Gibson, Royal Prince Alfred Hospital, Sydney, Australia

Sergio Giralt, MD Anderson Cancer Center, Houston, Texas, USA

Hartmut Goldschmidt, University Hospital Heidelberg, Heidelberg, Germany

Philip Greipp, Mayo Clinic, Rochester, Minnesota, USA

Roman Hajek, Brno University, Brno, Czech Republic

Izhar Hardan, Tel Aviv University, Tel Aviv, Israel

Jean-Luc Harousseau, Institute de Biologie, Nantes, France

Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan

Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan

Tom Heffner, Emory University, Atlanta, Georgia, USA

Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia

Vania Hungria, Clinica San Germano, Sao Paolo, Brazil

Shinsuke Ida, Nagoya City University Medical School, Nagoya, Japan

Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South Africa

Sundar Jagannath, St Vincent's Comprehensive Cancer Center, New York, New York, USA

Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China

Douglas Joshua, Royal Prince Alfred Hospital, Sydney, Australia

Artur Jurczyszyn, The Myeloma Treatment Foundation, Poland

Michio Kawano, Yamaguchi University, Ube, Japan

Nicolaus Kröger, University Hospital Hamburg, Hamburg, Germany

Shaji Kumar, Department of Hematology, Mayo Clinic, Minnesota, USA

Robert A Kyle, Department of Laboratory Med. and Pathology, Mayo Clinic, Minnesota, USA

Juan Lahuerta, Grupo Espanol di Mieloma, Hospital Universitario, Madrid, Spain

Ola Landgren, National Cancer Institute, Bethesda, Maryland, USA

Jacob Laubach, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea

Xavier LeLeu, Hospital Huriez, CHRU Lille, France

Suzanne Lentzsch, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Henk Lokhorst, University Medical CenterUtrecht, Utrecht, The Netherlands

Sagar Lonial, Emory University Medical School, Atlanta, Georgia, USA

Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria

Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil

Maria Mateos, University of Salamanca, Salamanca, Spain

Jayesh Mehta, Northwestern University, Chicago, Illinois, USA

Ulf-Henrik Mellqvist, Sahlgrenska University Hospital, Gothenburg, Sweden

GiamPaolo Merlini, University of Pavia, Pavia, Italy

Joseph Mikhael, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Angelina Rodriquez Morales, Bonco Metro Politano de Sangre, Caracas, Venezuela

Philippe Moreau, University Hospital, Nantes, France

Gareth Morgan, Royal Marsden Hospital, London, England

Nikhil Munshi, Diane Farber Cancer Institute, Boston, Massachusetts, USA

Ruben Niesvizky, Weill Medical College of Cornell University, New York, New York, USA

Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela

Yana Novis, Hospital SírioLibanês, Bela Vista, Brazil

Robert Orlowski, MD Anderson Cancer Center, Houston, Texas, USA

Antonio Palumbo, Cathedra Ematologia, Torino, Italy

Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina

Linda Pilarski, University of Alberta, Alberta, Canada

Raymond Powles, Leukemia & Myeloma, Wimbledon, England

S Vincent Rajkumar, Mayo Clinic, Rochester, Minnesota, USA

Donna Reece, Princess Margaret Hospital, Toronto, Canada

Tony Reiman, Cross Cancer Institute, Alberta, Canada

Paul G Richardson, Dana Farber Cancer Institute, Boston, Massachusetts, USA

David Roodman, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania USA

Laura Rosinol, Hospital Clinic, Barcelona, Spain

Jesus San Miguel, University of Salamanca, Salamanca, Spain

Orhan Sezer, Universitätsklinik Würzburg, Würzburg, Germany

Jatin J Shah, MD Anderson Cancer Institute, Houston, Texas, USA

John Shaughnessy, MIRT UAMS, Little Rock, Arkansas, USA

Kazuyuki Shimizu, Nagoya City Midori General Hospital, Nagoya, Japan

Chaim Shustik, McGill University, Montreal, Canada

David Siegel, Hackensack, Cancer Center, Hackensack, New Jersey, USA

Seema Singhal, Northwestern University, Chicago, Illinois, USA

Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands

Andrew Spencer, The Alfred Hospital, Melbourne, Australia

Edward Stadtmauer, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Keith Stewart, Mayo Clinic Arizona, Scottsdale, Arizona, USA

Evangelos Terpos, University of Athens School of Medicine, Athens, Greece

Patrizia Tosi, Italian Cooperative Group, Istituto di Ematologia Seragnoli, Bologna, Italy

Guido Tricot, Huntsman Cancer Institute, Salt Lake City, Utah, USA

Ingemar Turesson, SKANE University Hospital, Malmo, Sweden

Karin Vanderkerken, Vrije University Brussels VUB, Brussels, Belgium

Brian Van Ness, University of Minnesota, Minneapolis, Minnesota, USA

Ivan Van Riet, Brussels Vrija University, Brussels, Belgium

Robert Vescio, Cedars-Sinai Cancer Center, Los Angeles, California, USA

David Vesole, Hackensack Cancer Center, Hackensack, New Jersey, USA

Anders Waage, University Hospital, Trondheim, Norway NSMG

Michael Wang, MD Anderson, Houston, Texas, USA

Donna Weber, MD Anderson, Houston, Texas, USA

Jan Westin, Sahlgrenska University Hospital, Gothenburg, Sweden

Keith Wheatley, University of Birmingham, Birmingham, United Kingdom

Dina B Yehuda, Department of Hematology, Hadassah University Hospital, Hadassah, Israel

Jeffrey Zonder, Karmanos Cancer Institute, Detroit, Michigan, USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kyle, R., Durie, B., Rajkumar, S. et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia 24, 1121–1127 (2010). https://doi.org/10.1038/leu.2010.60

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2010.60

Keywords

This article is cited by

Search

Quick links