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Monoclonal gammopathy of undetermined significance

Last reviewed: 30 Mar 2025
Last updated: 10 May 2023

Summary

Definition

History and exam

Key diagnostic factors

  • at-risk demographic (male, age >50 years, African ancestry)
  • clinically asymptomatic
  • positive family history
  • history of radiation exposure
  • history of pesticide exposure
Full details

Other diagnostic factors

  • history of immunosuppression or infections
  • presence of peripheral neuropathy
Full details

Risk factors

  • male sex
  • age >50 years
  • African ancestry
  • family history of MGUS or multiple myeloma
  • immune-mediated conditions
  • radiation exposure
  • pesticide exposure
Full details

Diagnostic tests

1st tests to order

  • electrophoresis with immunofixation and measurement of serum immunoglobulins
  • CBC with differential
  • serum calcium
  • serum creatinine
  • urinalysis and 24-hour urine collection with electrophoresis and immunofixation
  • serum free light chains assay
  • metastatic bone survey (conventional x-ray or whole body low-dose CT scan)
Full details

Tests to consider

  • bone marrow aspiration and/or biopsy
  • bone mineral density scan
  • MRI scan
  • PET scan
Full details

Treatment algorithm

ONGOING

confirmed MGUS

Contributors

Authors

Shaji Kumar, MD

Professor of Medicine

Division of Hematology

Mayo Clinic

Rochester

MN

Disclosures

SK has received research funding for clinical trials to the institution from Abbvie, Amgen, Allogene, Astra-Zeneca, BMS, Carsgen, GSK, Janssen, Novartis, Roche-Genentech, Takeda and Regeneron. SK has participated in consulting and advisory board activities (with no personal payments) for Abbvie, Amgen, BMS, Janssen, Roche-Genentech, Takeda, Astra-Zeneca, Bluebird Bio, Secura Biotherapeutics, Trillium, Loxo Oncology, K36, Sanofi, ArcellX, and (with personal payment) Oncopeptides, Beigene and Antengene.

Acknowledgements

Professor Shaji Kumar would like to gratefully acknowledge Dr Ola Landgren, a previous contributor to this topic.

Disclosures

OL is an author of several references cited in this topic.

Peer reviewers

Daniel Catovsky, MD

Consultant Haemato-Oncologist

Section of Haemato-Oncology

Brookes Lawley Institute of Cancer

Sutton

UK

Disclosures

DC declares that he has no competing interests.

References

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Key articles

Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48.Full text  Abstract

van de Donk NW, Palumbo A,R Johnsen HE, et al. The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders: recommendations from the European Myeloma Network. Haematologica. 2014 Jun;99(6):984-96.Full text  Abstract

Bird J, Behrens J, Westin J, et al. UK Myeloma Forum (UKMF) and Nordic Myeloma Study Group (NMSG): guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol. 2009 Oct;147(1):22-42.Full text  Abstract

Kyle RA, Durie BG, Rajkumar SV, et al; International Myeloma Working Group. 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. 2010 Jun;24(6):1121-7.Full text  Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.
  • Monoclonal gammopathy of undetermined significance images
  • Differentials

    • Multiple myeloma or smoldering myeloma
    • Amyloidosis
    • Waldenström macroglobulinemia
    More Differentials
  • Guidelines

    • International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
    • The clinical relevance and management of monoclonal gammopathy of undetermined significance and related disorders
    More Guidelines
  • Patient information

    Monoclonal gammopathy of undetermined significance

    More Patient information
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