Prevalence of monoclonal gammopathy of undetermined significance
Open accessAbstract
BACKGROUND: The prevalence of monoclonal gammopathy of undetermined significance (MGUS), a premalignant plasma-cell disorder, among persons 50 years of age or older has not been accurately determined. We used sensitive laboratory techniques to ascertain the prevalence of MGUS in a large population in a well-defined geographic area. METHODS: We identified all living residents of Olmsted County, Minnesota, as of January 1, 1995. We obtained serum that remained after the performance of routine clinical tests at Mayo Clinic or asked subjects for whom such serum was unavailable to provide a sample. Agarose-gel electrophoresis was performed on all serum samples, and any serum sample with a discrete band of monoclonal protein or thought to have a localized band was subjected to immunofixation. RESULTS: Serum samples were obtained from 21,463 of the 28,038 enumerated residents 50 years of age or older (76.6 percent). MGUS was identified in 694 (3.2 percent) of these persons. Age-adjusted rates were higher in men than in women (4.0 percent vs. 2.7 percent, P<0.001). The prevalence of MGUS was 5.3 percent among persons 70 years of age or older and 7.5 percent among those 85 years of age or older. The concentration of monoclonal immunoglobulin was less than 1.0 g per deciliter in 63.5 percent and at least 2.0 g per deciliter in only 4.5 percent of 694 persons. The concentration of uninvolved immunoglobulins was reduced in 27.7 percent of 447 persons tested, and 21.5 percent of 79 tested had a monoclonal urinary light chain. CONCLUSIONS: Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.
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Multiple myeloma does not develop rapidly; symptoms and organ damage may take decades to manifest.
“This tumor does not develop rapidly; instead, it may take decades for symptoms and organ damage to manifest.4-8”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
The Results (page unavailable) describe MGUS as a premalignant precursor of myeloma and report progression to myeloma or a related malignancy at about 1% per year, with risks calculated over 20 years. This supports the possibility of a long precursor phase, but the paper does not establish that symptoms and organ damage from multiple myeloma take decades to manifest. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAll cases of multiple myeloma are preceded by precursor conditions such as smoldering multiple myeloma and monoclonal gammopathy of undetermined significance, often decades before diagnosis.
“MM is well-described to be universally preceded by precursor states, often decades before it is even diagnosed.”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
The Results identify MGUS as a premalignant precursor of myeloma and describe its continuing risk of progression. They do not establish that every case of multiple myeloma has a precursor state, or that such a state is often present decades before diagnosis; the reported 20-year risks concern time since MGUS diagnosis, not time before myeloma diagnosis. No page number is available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPatients with MGUS and SMM might experience progression to multiple myeloma over an extremely variable timeframe, with some progressing within 2 years, others after 10 to 20 years, or never.
“Several epidemiological studies have shown that patients with MGUS and SMM might experience progression to MM over an extremely variable timeframe. Some patients progressed to MM within 2 years of diagnosis, while others may progress after 10 to 20 years or might never progress at all.4-6,75”
From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [5]
The Results report an approximately 1% annual risk of progression for MGUS and different risks 20 years after diagnosis; the Discussion says patients with MGUS require indefinite monitoring. This supports variable progression risk and the possibility of not progressing, but the paper does not give the claimed individual timelines of 2 or 10–20 years or establish them for SMM. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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“The percentage of each type of M protein is shown in samples from patients with MGUS [21], myeloma [22], and AL amyloidosis [23].”
Rajkumar, S. V., Gupta, V, Fonseca, R., Dispenzieri, A., Gonsalves, W. I., Larson, D., Ketterling, R. P., Lust, J. A., Kyle, R. A., & Kumar, S. K. (2013) · Leukemia · doi:10.1038/leu.2013.86 · Cited by 239 · see citing works
Self-citationThe Diagnosis and Treatment of Multiple Myeloma
Gerecke, C., Fuhrmann, S., Strifler, S., Schmidt‐Hieber, M., Einsele, H., & Knop, S. T. (2016) · Deutsches Ärzteblatt international · doi:10.3238/arztebl.2016.0470 · Cited by 241 · see citing works
Landgren, O., & Weiss, B. M. (2009) · Leukemia · doi:10.1038/leu.2009.134 · Cited by 231 · see citing works
Clinically relevant end points and new drug approvals for myeloma
Anderson, K. C., Kyle, R. A., Rajkumar, S. V., Stewart, A. K., Weber, D. M., & Richardson, P. G. G. (2007) · Leukemia · doi:10.1038/sj.leu.2405016 · Cited by 225 · see citing works
Self-citationMonoclonal gammopathy of undetermined significance
Kyle, R. A., & Rajkumar, S. V. (2006) · British Journal of Haematology · doi:10.1111/j.1365-2141.2006.06235.x · Cited by 223 · see citing works
“The first population-based study using the sensitive laboratory techniques to detect monoclonal gammopathies was recently reported (Kyle et al, 2006).”
BackgroundSelf-citationSethi, S. M., & Fervenza, F. C. (2011) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2011.06.005 · Cited by 215 · see citing works
Immunotherapy of multiple myeloma
Minnie, S. A., & Hill, G. R. (2020) · Journal of Clinical Investigation · doi:10.1172/jci129205 · Cited by 216 · see citing works
“Interestingly, MM often progresses from a premalignant state, monoclonal gammopathy of undetermined significance (MGUS), that displays a lifelong rate of progression of 1% per year (3, 4).”
BackgroundMonoclonal Gammopathy of Renal Significance
Leung, N., Bridoux, F., & Nasr, S. H. (2021) · New England Journal of Medicine · doi:10.1056/nejmra1810907 · Cited by 213 · see citing works
Multiple myeloma: 2018 update on diagnosis, risk‐stratification, and management
Rajkumar, S. V. (2018) · American Journal of Hematology · doi:10.1002/ajh.25117 · Cited by 228 · see citing works
Self-citationMultiple myeloma: 2014 Update on diagnosis, risk‐stratification, and management
Rajkumar, S. V. (2014) · American Journal of Hematology · doi:10.1002/ajh.23810 · Cited by 214 · see citing works
Self-citationLandgren, O., Graubard, B. I., Katzmann, J. A., Kyle, R. A., Ahmadizadeh, I., Clark, R. J., Kumar, S. K., Dispenzieri, A. A., Greenberg, A. J., Therneau, T. M., et al. (2014) · Leukemia · doi:10.1038/leu.2014.34 · Cited by 209 · see citing works
Self-citationBida, J. P., Kyle, R. A., Therneau, T. M., Melton, L. J., Plevak, M. F., Larson, D. R., Dispenzieri, A. A., Katzmann, J. A., & Rajkumar, S. V. (2009) · Mayo Clinic Proceedings · doi:10.4065/84.8.685 · Cited by 202 · see citing works
Self-citationMailankody, S., Pfeiffer, R. M., Kristinsson, S. Y., Korde, N., Björkholm, M., Goldin, L. R., Turesson, I., & Landgren, O. (2011) · Blood · doi:10.1182/blood-2011-05-355743 · Cited by 201 · see citing works
Korde, N., Kristinsson, S. Y., & Landgren, O. (2011) · Blood · doi:10.1182/blood-2011-01-270140 · Cited by 199 · see citing works
Špíšek, R., Kukreja, A., Chen, L.-C., Matthews, P., Mazumder, A., Vesole, D. H., Jagannath, S., Zebroski, H. A., Simpson, A. J. G., Ritter, G., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20062387 · Cited by 199 · see citing works
Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma
Kristinsson, S. Y., Fears, T. R., Gridley, G., Turesson, I., Mellqvist, U., Björkholm, M., & Landgren, O. (2008) · Blood · doi:10.1182/blood-2008-04-151076 · Cited by 198 · see citing works
Prevalence of Monoclonal Gammopathy of Undetermined Significance Among Men in Ghana
Landgren, O., Katzmann, J. A., Hsing, A. W., Pfeiffer, R. M., Kyle, R. A., Yeboah, E. D., Biritwum, R. B., Tettey, Y., Adjei, A. A., Larson, D. R., et al. (2007) · Mayo Clinic Proceedings · doi:10.1016/s0025-6196(11)61089-6 · Cited by 194 · see citing works
Self-citationMcKenna, R. W., & Linden, M. A. (2015) · Springer eBooks · doi:10.1007/978-3-319-10918-3 · Cited by 194 · see citing works
Strauss‐Albee, D. M., Fukuyama, J., Liang, E. C., Yao, Y., Jarrell, J. A., Drake, A. L., Kinuthia, J., Montgomery, R. R., John-Stewart, G. C., Holmes, S., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac5722 · Cited by 188 · see citing works
“T and B cell diversity peaks early in life and decreases with age, as oligoclonal memory populations of both T and B cells pervade, diminishing diversity for both TCR (35, 36) and immunoglobulin (37, 38).”
BackgroundRajkumar, S. V., Dispenzieri, A. A., & Kyle, R. A. (2006) · Mayo Clinic Proceedings · doi:10.4065/81.5.693 · Cited by 192 · see citing works
Self-citationGenetic events in the pathogenesis of multiple myeloma
Chng, W. J., Glebov, O. K., Bergsagel, P. L., & Kuehl, W. M. (2007) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2007.08.004 · Cited by 189 · see citing works
C3 Glomerulonephritis Associated With Monoclonal Gammopathy: A Case Series
Zand, L., Kattah, A. G., Fervenza, F. C., Smith, R. J., Nasr, S. H., Zhang, Y., Vrana, J. A., Leung, N., Cornell, L. D., & Sethi, S. M. (2013) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2013.02.370 · Cited by 181 · see citing works
Membranoproliferative Glomerulonephritis Secondary to Monoclonal Gammopathy
Sethi, S. M., Zand, L., Leung, N., Smith, R. J., Jevremonic, D., Herrmann, S. M., & Fervenza, F. C. (2010) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.06760909 · Cited by 181 · see citing works
“In addition, two of three patients with negative SPEP studies had monoclonal/biclonal bands on SIFE.”
BackgroundInfluentialvan de Donk, N. W. C. J., Palumbo, A. P., Johnsen, H. E., Engelhardt, M. M., Gay, F., Gregersen, H., Hájek, R., Kleber, M., Ludwig, H., Morgan, G. J., et al. (2014) · Haematologica · doi:10.3324/haematol.2013.100552 · Cited by 175 · see citing works
“immunoglobulin light-chain (AL) amyloidosis, chronic lymphocytic leukemia (CLL), or B-cell lymphoma.(3,4) For IgM”
BackgroundMGUS to myeloma: a mysterious gammopathy of underexplored significance
Dhodapkar, M. V. (2016) · Blood · doi:10.1182/blood-2016-09-692954 · Cited by 175 · see citing works
Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review
Wadhera, R. K., & Rajkumar, S. V. (2010) · Mayo Clinic Proceedings · doi:10.4065/mcp.2010.0337 · Cited by 170 · see citing works
Self-citationKidney Disease and Multiple Myeloma
Heher, E. C., Rennke, H. G., Laubach, J. P., & Richardson, P. G. G. (2013) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.12231212 · Cited by 169 · see citing works
Ageing is associated with diminished apoptotic cell clearancein vivo
Aprahamian, T. R., Takemura, Y., Goukassian, D. A., & Walsh, K. (2008) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2008.03658.x · Cited by 168 · see citing works
Landgren, O., Kristinsson, S. Y., Goldin, L. R., Caporaso, N. E., Blimark, C. H., Mellqvist, U., Wåhlin, A., Björkholm, M., & Turesson, I. (2009) · Blood · doi:10.1182/blood-2008-12-191676 · Cited by 167 · see citing works
Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR)
Phull, P. M., Sanchorawala, V., Connors, L. H., Doros, G. D., Ruberg, F. L., Berk, J. L., & Sarosiek, S. (2018) · Amyloid · doi:10.1080/13506129.2018.1436048 · Cited by 167 · see citing works
“3% in patients greater than 70 years of age [19].”
BackgroundSerum proteins and their diagnostic utility in veterinary medicine: a review
Tóthová, C., Nagy, O., & Kovác, G. (2016) · Veterinární Medicína · doi:10.17221/19/2016-vetmed · Cited by 164 · see citing works
“A broad-based peak (arrow) is present in the g-region order present in more than 3% of the general human population at the age of 50 years and older (Kyle et al. 2006).”
BackgroundMorbidity and Mortality Among Older Individuals With Undiagnosed Celiac Disease
Godfrey, J. D., Brantner, T. L., Brinjikji, W., Christensen, K., Brogan, D. L., Dyke, C. T. V., Lahr, B. D., Larson, J. J., Rubio‐Tapia, A., Melton, L. J., et al. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.05.041 · Cited by 163 · see citing works
Self-citationThe Complexity and Heterogeneity of Monoclonal Immunoglobulin–Associated Renal Diseases
Sethi, S. M., Rajkumar, S. V., & D’Agati, V. D. (2018) · Journal of the American Society of Nephrology · doi:10.1681/asn.2017121319 · Cited by 163 · see citing works
Self-citationLandgren, O., Rajkumar, S. V., Pfeiffer, R. M., Kyle, R. A., Katzmann, J. A., Dispenzieri, A. A., Cai, Q., Goldin, L. R., Caporaso, N. E., Fraumeni, J. F., et al. (2010) · Blood · doi:10.1182/blood-2010-01-262394 · Cited by 162 · see citing works
Self-citationMultiple myeloma: 2013 update on diagnosis, risk‐stratification, and management
Rajkumar, S. V. (2013) · American Journal of Hematology · doi:10.1002/ajh.23390 · Cited by 157 · see citing works
Self-citationAssociated conditions in small fiber neuropathy – a large cohort study and review of the literature
de Greef, B. T. A., Hoeijmakers, J. G. J., Gorissen-Brouwers, C. M. L., Geerts, M., Faber, C. G., & Merkies, I. S. J. (2017) · European Journal of Neurology · doi:10.1111/ene.13508 · Cited by 156 · see citing works
Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management
Rajkumar, S. V. (2011) · American Journal of Hematology · doi:10.1002/ajh.21913 · Cited by 152 · see citing works
Self-citationMonoclonal Gammopathy–Associated Peripheral Neuropathy: Diagnosis and Management
Chaudhry, H. M., Mauermann, M. L., & Rajkumar, S. V. (2017) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2017.02.003 · Cited by 152 · see citing works
“Approximately half of these associations are likely coincidental, since MGUS is prevalent in 3% to 4% of the normal adult population over 50 years of age.(5) The remaining associations may be causally related to the underlying M protein.”
BackgroundSelf-citationVachon, C. M., Kyle, R. A., Therneau, T. M., Foreman, B. J., Larson, D. R., Colby, C. L., Phelps, T. K., Dispenzieri, A. A., Kumar, S. K., Katzmann, J. A., et al. (2009) · Blood · doi:10.1182/blood-2008-12-192575 · Cited by 152 · see citing works
Self-citationDissecting racial disparities in multiple myeloma
Marinac, C. R., Ghobrial, I. M., Birmann, B. M., Soiffer, J. L., & Rebbeck, T. R. (2020) · Blood Cancer Journal · doi:10.1038/s41408-020-0284-7 · Cited by 150 · see citing works
The ageing B cell population: Composition and function
Ademokun, A., Wu, Y.-C. B., & Dunn‐Walters, D. K. (2009) · Biogerontology · doi:10.1007/s10522-009-9256-9 · Cited by 146 · see citing works
“Data looking at individual clonal responses and accumulation of mutations in both splenic and Peyers Patch germinal centres in man indicate that there are no changes in the fundamental mechanism of SHM with age (Banerjee et al. 2002; Kolar et al. 2006; Rosner et al. 2001) but rather differences may occur as a result o…”
Sigurdardottir, E. E., Turesson, I., Lund, S. H., Lindqvist, E. K., Mailankody, S., Korde, N., Björkholm, M., Landgren, O., & Kristinsson, S. Y. (2015) · JAMA Oncology · doi:10.1001/jamaoncol.2015.23 · Cited by 146 · see citing works
Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study
Kristinsson, S. Y., Tang, M., Pfeiffer, R. M., Björkholm, M., Goldin, L. R., Blimark, C. H., Mellqvist, U. H., Wåhlin, A., Turesson, I., & Landgren, O. (2011) · Haematologica · doi:10.3324/haematol.2011.054015 · Cited by 146 · see citing works
“In MGUS, prior studies report that hypogammaglobulinemia is present in 25-28% of the cases.(9,16) Interestingly, in contrast to MM and WM, in the MGUS study from Denmark, presence of hypogammaglobulinemia was not associated with an increased risk of bacteremia.”
ResultLandgren, O., Kyle, R. A., Hoppin, J. A., Beane Freeman, L. E., Cerhan, J. R., Katzmann, J. A., Rajkumar, S. V., & Alavanja, M. C. (2009) · Blood · doi:10.1182/blood-2009-02-203471 · Cited by 166 · see citing works
Self-citationEpidemiology of the plasma-cell disorders
Kyle, R. A., & Rajkumar, S. V. (2007) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2007.08.001 · Cited by 145 · see citing works
Self-citationRecurrent membranoproliferative glomerulonephritis after kidney transplantation
Lorenz, E. C., Sethi, S. M., Leung, N., Dispenzieri, A. A., Fervenza, F. C., & Cosio, F. G. (2010) · Kidney International · doi:10.1038/ki.2010.1 · Cited by 144 · see citing works
Self-citationHow I manage monoclonal gammopathy of undetermined significance
Go, R. S., & Rajkumar, S. V. (2017) · Blood · doi:10.1182/blood-2017-09-807560 · Cited by 141 · see citing works
“3% among those <50 years.(2,3) There is a higher risk and earlier age of onset in blacks compared to whites.”
BackgroundSelf-citationTuresson, I., Kovalchik, S. A., Pfeiffer, R. M., Kristinsson, S. Y., Goldin, L. R., Drayson, M. T., & Landgren, O. (2013) · Blood · doi:10.1182/blood-2013-05-505487 · Cited by 140 · see citing works
“Data from the Mayo Clinic suggest that MGUS is present in ;3% of the general white population $50 years of age and is predominantly incidentally diagnosed.(7,8) Although 2 independent studies indicate that MGUS always precedes MM,(9,10) the majority ofMGUS patients do not progress to a lymphoproliferative disorder.”
BackgroundCardiac transthyretin amyloidosis
Dungu, J. N., Anderson, L. J., Whelan, C. J., & Hawkins, P. N. (2012) · Heart · doi:10.1136/heartjnl-2012-301924 · Cited by 140 · see citing works
“The presence of a monoclonal gammopathy had often been misleading in this series, suggesting AL amyloidosis, but it is important to appreciate that incidental monoclonal gammopathy of undetermined significance (MGUS) occurs in over 5% of persons aged over 70 years.(31) The reported increased risk of MGUS in Afro-Carib…”
Background
- Authors
- Kyle, R. A., Therneau, T. M., Rajkumar, S. V., Larson, D. R., Plevak, M. F., Offord, J. R., Dispenzieri, A., Katzmann, J. A., & Melton, L. J.
- Affiliations
- Mayo Clinic (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2006-03-30
- Volume
- 354
- Issue
- 13
- Pages
- 1362-1369
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2086990334
- Cited by
- 1,423
- References
- 22
- Citations by year
- 2026: 56 · 2025: 80 · 2024: 90 · 2023: 71 · 2022: 83 · 2021: 88 · 2020: 93 · 2019: 77 · 2018: 64 · 2017: 73 · 2016: 66 · 2015: 60 · 2014: 66 · 2013: 78 · 2012: 70
- FWCI
- 33.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 107 476, CA6 2242, R01CA107476, P01CA062242)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- monoclonal gammopathy of undetermined significance, prevalence, plasma cell dyscrasia, M protein, serum protein electrophoresis, immunofixation, age differences, Olmsted County, Minnesota
- MeSH terms
- Aged, Aged, 80 and over, Female, Humans, Immunoglobulin A, Immunoglobulin G, Immunoglobulin M, Male, Middle Aged, Minnesota, Paraproteinemias, Prevalence, Age Distribution, Sex Distribution
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