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Cited by 93Multiple Myeloma Research and TreatmentsAmyloidosis: Diagnosis, Treatment, OutcomesGlobal Cancer Incidence and Screening

Prevalence of smoldering multiple myeloma based on nationwide screening

Open access
Thorsteinsdóttir, Sigrún, Gíslason, Gauti K., Aspelund, Thor, Rögnvaldsson, Sæmundur, Óskarsson, Jón Þórir, Sigurðardóttir, Guðrún Á, Þórðardóttir, Ásdís R., Viðarsson, Brynjar +14 more·2023·Nature Medicine
DOI 10.1038/s41591-022-02183-6PMC PMC11099842
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Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to multiple myeloma. Here we define the epidemiological characteristics of SMM in the general population in Iceland. The iStopMM study (ClinicalTrials.gov ID: NCT03327597 ) is a nationwide screening study for multiple myeloma precursors where all residents in Iceland 40 years or older were invited to participate. SMM was defined as 10-60% bone marrow plasma cells and/or monoclonal (M) protein concentration ≥3 g dl-1, in the absence of myeloma-defining events. Of the 80,759 who gave informed consent to participate, 75,422 (93%) were screened. The prevalence of SMM in the total population was 0.53% (95% confidence interval (CI) = 0.49-0.57%) in individuals 40 years or older. In men and women, the prevalence of SMM was 0.67% (95% CI = 0.62-0.73%) and 0.39% (95% CI = 0.35-0.43%), respectively; it increased with age in both sexes. For the 193 individuals with SMM, median age was 70 years (range 44-92 years) and 60% were males. The mean M protein concentration of individuals with SMM was 0.62 g dl-1 (range 0.01-3.5 g dl-1) and 73% had 11-20% bone marrow plasma cell infiltration. The high prevalence of SMM has implications for future treatment policies in multiple myeloma as the evidence supporting treatment initiation at the SMM stage is emerging.

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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 [8]

    The Discussion (page unavailable) says some people with smoldering multiple myeloma have an indolent condition that progresses very slowly or not at all, and discusses treatment before end-organ damage. It does not say that symptoms and organ damage may take decades to appear, or establish that timeline for multiple myeloma generally. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • RAS mutations, MYC translocations, APOBEC mutagenesis, and patterns of genomic complexity are the most commonly reported alterations in progressing multiple myeloma.

    “Among these, RAS mutations, MYC translocations, APOBEC mutagenesis, and patterns of genomic complexity are the most commonly reported.8,9,11,69,76-83,84”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [8]

    The Discussion (page not provided) says that whole-genome sequencing analyses of progressive and stable disease are ongoing; it does not report which genomic alterations are most common. Searches for RAS mutations, MYC translocations, APOBEC mutagenesis, and genomic complexity found no passage in our copy addressing that claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Cites

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Authors
Thorsteinsdóttir, S., Gíslason, G. K., Aspelund, T., Rögnvaldsson, S., Óskarsson, J. Þ., Sigurðardóttir, G. Á., Þórðardóttir, Á. R., Viðarsson, B., Önundarson, P. T., Agnarsson, B. A., Sigurðardóttir, M., Þorsteinsdóttir, I., Ólafsson, Í., Eyþórsson, E., Jónsson, Á., Berlanga, O., Hultcrantz, M., Durie, B. G. M., Löve, T. J., Harding, S., Landgren, O., & Kristinsson, S. Y.
Affiliations
  • University of Iceland (IS)
  • National University Hospital of Iceland (IS)
  • Memorial Sloan Kettering Cancer Center (US)
  • Cedars-Sinai Medical Center (US)
  • University of Miami (US)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-02
Volume
29
Issue
2
Pages
467-472
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-022-02183-6
PMC
PMC11099842
OpenAlex
W4319310767
Cited by
93
References
2
Citations by year
2026: 27 · 2025: 29 · 2024: 27 · 2023: 9
FWCI
19.00
Type
journal article
Language
en
Update notices
correction (2023-03-20)
Open access
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • European Commission (716677, HORIZON2020)
  • Háskóli Íslands
  • National Cancer Institute (P30CA008748)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
  • Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
Keywords
smoldering multiple myeloma, prevalence, monoclonal protein, bone marrow plasma cells, Iceland, sex differences, age-related risk
MeSH terms
Smoldering Multiple Myeloma, Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Multiple Myeloma, Risk Factors, Prevalence, Disease Progression

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