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Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance
Open accessAbstract
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in approximately 3% of persons 50 years of age or older. METHODS: We studied 1384 patients who were residing in southeastern Minnesota and in whom MGUS was diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was progression to multiple myeloma or another plasma-cell or lymphoid disorder. RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as high as the rate in the control population. The risk of progression without accounting for death due to competing causes was 10% at 10 years, 18% at 20 years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (≥1.5 g per deciliter) - was associated with a risk of progression at 20 years of 55%, as compared with 41% among patients who had one adverse risk factor and 19% among patients who had neither risk factor. Among patients with non-IgM MGUS, the risk of progression at 20 years was 30% among those who had the two risk factors, 20% among those who had one risk factor, and 7% among those who had neither risk factor. Patients with MGUS had shorter survival than was expected in the control population of Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001). CONCLUSIONS: Significant differences were noted in the risk of progression between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was shorter among patients with MGUS than was expected in a matched control population. (Funded by the National Cancer Institute.).
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“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 [4]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“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 [4]
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“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 [4]
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“MGUS progresses to multiple myeloma or related malignancy a rate of 1% per year.16,17”
From Multiple myeloma: 2024 update on diagnosis, risk-stratification, and management (2024) · cites this paper as [17]
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Additional file 2 of A gene signature can predict risk of MGUS progressing to multiple myeloma
Sun, F., Cheng, Y., Ying, J., Mery, D. E., Al Hadidi, S., Wanchai, V., Siegel, E. R., Xu, H., Gai, D., Ashby, T. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26600785
Additional file 3 of A gene signature can predict risk of MGUS progressing to multiple myeloma
Sun, F., Cheng, Y., Ying, J., Mery, D. E., Al Hadidi, S., Wanchai, V., Siegel, E. R., Xu, H., Gai, D., Ashby, T. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26600788
Additional file 1 of A gene signature can predict risk of MGUS progressing to multiple myeloma
Sun, F., Cheng, Y., Ying, J., Mery, D. E., Al-Hadidi, S., Wanchai, V., Siegel, E. R., Xu, H., Gai, D., Ashby, T. C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26600782
Huebner, M., Vach, W., le Cessie, S., Schmidt, C. O., & Lusa, L. (2020) · Figshare · doi:10.6084/m9.figshare.11984637
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Bystander or perpetrator: Unravelling the significance and challenges of MGUS
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Immunoglobulin Light Chain Amyloidosis
Bhatt, M., Jevremović, D., & Rajkumar, S. V. (2026) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2025.08.016
Self-citation
Metadata
- Authors
- Kyle, R. A., Larson, D. R., Therneau, T. M., Dispenzieri, A., Kumar, S., Cerhan, J. R., & Rajkumar, S. V.
- Affiliations
- Mayo Clinic (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-01-18
- Volume
- 378
- Issue
- 3
- Pages
- 241-249
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5852672
- OpenAlex
- W2785817645
- Cited by
- 647
- References
- 30
- Citations by year
- 2026: 62 · 2025: 90 · 2024: 101 · 2023: 81 · 2022: 75 · 2021: 76 · 2020: 80 · 2019: 47 · 2018: 33
- FWCI
- 42.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA107476, CA168762, CA186781)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Internal Medicine › Amyloidosis: Diagnosis, Treatment, Outcomes
- Keywords
- monoclonal gammopathy of undetermined significance, progression to multiple myeloma, plasma cell dyscrasia, free light chain ratio, risk factors, survival, long-term follow-up
- MeSH terms
- Adult, Aged, Bone Marrow Examination, Female, Follow-Up Studies, Glycoproteins, Humans, Immunoglobulin M, Immunoglobulin Light Chains, Male, Middle Aged, Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, Prognosis, Risk Factors, Proportional Hazards Models, Disease Progression
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