CoChat
Sign Up
Cited by 291Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchAmyloidosis: Diagnosis, Treatment, Outcomes

International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM)

Open access
Mateos, María-Victoria, Kumar, Shaji, Dimopoulos, Meletios A., González-Calle, Verónica, Kastritis, Efstathios, Hajek, Roman, De Larrea, Carlos Fernández, Morgan, Gareth J. +21 more·2020·Blood Cancer Journal
DOI 10.1038/s41408-020-00366-3PMC PMC7567803
Open this paper in CoChat — free accountOpen PDF

Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic precursor state of multiple myeloma (MM). Recently, MM was redefined to include biomarkers predicting a high risk of progression from SMM, thus necessitating a redefinition of SMM and its risk stratification. We assembled a large cohort of SMM patients meeting the revised IMWG criteria to develop a new risk stratification system. We included 1996 patients, and using stepwise selection and multivariable analysis, we identified three independent factors predicting progression risk at 2 years: serum M-protein >2 g/dL (HR: 2.1), involved to uninvolved free light-chain ratio >20 (HR: 2.7), and marrow plasma cell infiltration >20% (HR: 2.4). This translates into 3 categories with increasing 2-year progression risk: 6% for low risk (38%; no risk factors, HR: 1); 18% for intermediate risk (33%; 1 factor; HR: 3.0), and 44% for high risk (29%; 2–3 factors). Addition of cytogenetic abnormalities (t(4;14), t(14;16), +1q, and/or del13q) allowed separation into 4 groups (low risk with 0, low intermediate risk with 1, intermediate risk with 2, and high risk with ≥3 risk factors) with 6, 23, 46, and 63% risk of progression in 2 years, respectively. The 2/20/20 risk stratification model can be easily implemented to identify high-risk SMM for clinical research and routine practice and will be widely applicable.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41408-020-00366-3

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A group of already transformed tumors can remain stable and controlled for years before progressing into symptomatic disease.

    “This evidence reinforces the idea that a group of already transformed tumors can remain stable and controlled for years before progressing into symptomatic disease.21,100,101”

    From Evolution of Multiple Myeloma from a Genomic Perspective (2026) · cites this paper as [101]

    The Introduction describes smoldering multiple myeloma as an asymptomatic stage that can progress to active disease, and Results > Survival outcomes reports a median time to progression of 6.4 years. The paper therefore supports years without progression in this specific condition, but it does not establish that the tumors were already transformed or biologically controlled, or extend the finding to tumors generally. No page numbers are available in our copy. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 22

  1. [1]Kyle RA Greipp PR Smoldering multiple myeloma N. Engl. J. Med. 1980 302 1347 1349 10.1056/NEJM198006123022405 7374679 · DOI
  2. [2]Rajkumar SV Landgren O Mateos MV Smoldering multiple myeloma Blood 2015 125 3069 3075 10.1182/blood-2014-09-568899 25838344 PMC4432003 · DOI
  3. [3]Kyle RA Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma N. Engl. J. Med. 2007 356 2582 2590 10.1056/NEJMoa070389 17582068 · DOI · Paper page
  4. [4]Dispenzieri A Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma Blood 2008 111 785 789 10.1182/blood-2007-08-108357 17942755 PMC2200851 · DOI
  5. [5]Perez-Persona E 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 10.1182/blood-2007-05-088443 17576818 · DOI · Paper page
  6. [7]Lonial S E3A06: Randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma J. Clin. Oncol. 2019 37 8001 8001 10.1200/JCO.2019.37.15_suppl.8001 · DOI · Paper page
  7. [8]Rajkumar SV International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma Lancet Oncol. 2014 15 e538 e548 10.1016/S1470-2045(14)70442-5 25439696 · DOI · Paper page
  8. [9]Zamagni E 18F-FDG PET/CT focal, but not osteolytic, lesions predict the progression of smoldering myeloma to active disease Leukemia 2016 30 417 422 10.1038/leu.2015.291 26490489 · DOI
  9. [11]Fernandez de Larrea C Evolving M-protein pattern in patients with smoldering multiple myeloma: impact on early progression Leukemia 2018 32 1427 1434 10.1038/s41375-018-0013-4 29463830 · DOI
  10. [12]Ravi P Changes in uninvolved immunoglobulins during induction therapy for newly diagnosed multiple myeloma Blood Cancer J. 2017 7 e569 10.1038/bcj.2017.46 28622306 PMC5584483 · DOI
  11. [13]Gonzalez-Calle V Bence Jones proteinuria in smoldering multiple myeloma as a predictor marker of progression to symptomatic multiple myeloma Leukemia 2016 30 2026 2031 10.1038/leu.2016.123 27133826 · DOI
  12. [14]Dhodapkar MV Clinical, genomic, and imaging predictors of myeloma progression from asymptomatic monoclonal gammopathies (SWOG S0120) Blood 2014 123 78 85 10.1182/blood-2013-07-515239 24144643 PMC3879908 · DOI · Paper page
  13. [15]Breiman L Random forests Mach. Learn. 2001 45 5 32 10.1023/A:1010933404324 · DOI · Paper page
  14. [16]Svetnik V Random forest: a classification and regression tool for compound classification and QSAR modeling J. Chem. Inf. Comp. Sci. 2003 43 1947 1958 10.1021/ci034160g 14632445 · DOI
  15. [17]Massaro JM Managing and analysing data from a large-scale study on Framingham offspring relating brain structure to cognitive function Stat. Med. 2004 23 351 367 10.1002/sim.1743 14716734 · DOI
  16. [18]Kyle RA Rajkumar SV Multiple myeloma N. Engl. J. Med. 2004 351 1860 1873 10.1056/NEJMra041875 15509819 · DOI
  17. [19]Kumar SK Rajkumar SV The multiple myelomas - current concepts in cytogenetic classification and therapy Nat. Rev. Clin. Oncol. 2018 15 409 421 10.1038/s41571-018-0018-y 29686421 · DOI · Paper page
  18. [20]Witzig TE A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma Leukemia 2013 27 220 225 10.1038/leu.2012.236 22902362 PMC3912579 · DOI
  19. [21]Rajkumar SV Thalidomide as initial therapy for early-stage myeloma Leukemia 2003 17 775 779 10.1038/sj.leu.2402866 12682636 · DOI
  20. [22]Lakshman A Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria Blood Cancer J. 2018 8 59 10.1038/s41408-018-0077-4 29895887 PMC5997745 · DOI
  21. [25]Manier S Kawano Y Bianchi G Roccaro AM Ghobrial IM Cell autonomous and microenvironmental regulation of tumor progression in precursor states of multiple myeloma Curr. Opin. Hematol. 2016 23 426 433 10.1097/MOH.0000000000000259 27101529 · DOI
  22. [26]Dhodapkar MV MGUS to myeloma: a mysterious gammopathy of underexplored significance Blood 2016 128 2599 2606 10.1182/blood-2016-09-692954 27737890 PMC5146746 · DOI

Cited by

Sorted by citations

Authors
Mateos, M.-V., Kumar, S., Dimopoulos, M. A., González-Calle, V., Kastritis, E., Hajek, R., De Larrea, C. F., Morgan, G. J., Merlini, G., Goldschmidt, H., Geraldes, C., Gozzetti, A., Kyriakou, C., Garderet, L., Hansson, M., Zamagni, E., Fantl, D., Leleu, X., Kim, B.-S., Esteves, G., Ludwig, H., Usmani, S., Min, C.-K., Qi, M., Ukropec, J., Weiss, B. M., Rajkumar, S. V., Durie, B. G. M., & San-Miguel, J.
Affiliations
  • Consejo Superior de Investigaciones Científicas (ES)
  • Mayo Clinic (US)
  • National and Kapodistrian University of Athens (GR)
  • NYU Langone’s Laura and Isaac Perlmutter Cancer Center (US)
  • University of Pavia (IT)
  • National Center for Tumor Diseases (DE)
  • Unidade Local de Saúde de Coimbra (PT)
  • University of Siena (IT)
  • London North West Healthcare NHS Trust (GB)
  • Pitié-Salpêtrière Hospital (FR)
  • Sahlgrenska University Hospital (SE)
  • University of Bologna (IT)
  • Hospital Italiano de Buenos Aires (AR)
  • Centre Hospitalier Universitaire de Poitiers (FR)
  • Hallym University Dongtan Sacred Heart Hospital (KR)
  • Hospital de Santa Maria (PT)
  • Wilhelminen Hospital (AT)
  • Levine Cancer Institute (US)
  • The Catholic University of Korea Seoul St. Mary's Hospital (KR)
  • Cedars-Sinai Medical Center (US)
Corresponding author
Kumar, Shaji
ORCID
Venue
Blood Cancer Journal
Publisher
Springer Science and Business Media LLC
Published
2020-10-16
Volume
10
Issue
10
Pages
102-102
ISSN
2044-5385 (ISSN-L)
DOI
10.1038/s41408-020-00366-3
PMC
PMC7567803
OpenAlex
W3093376706
Cited by
291
References
4
Citations by year
2026: 47 · 2025: 67 · 2024: 52 · 2023: 39 · 2022: 49 · 2021: 35 · 2020: 1
FWCI
19.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Blood Cancer Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
  • Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by)
  • Lund University Publications (Lund University) (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion, cc-by)
Funders
Janssen Research and Development
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
smoldering multiple myeloma, risk stratification, progression risk, International Myeloma Working Group criteria, serum M-protein, free light chain ratio, bone marrow plasma cell infiltration, chromosomal abnormalities, del(13q)
MeSH terms
Aged, Female, Follow-Up Studies, Humans, Immunoglobulin Light Chains, Male, Middle Aged, Models, Biological, Multiple Myeloma, Myeloma Proteins, Risk Factors, Biomarkers, Tumor, Disease Progression

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review