Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial
(2024) In Annals of Internal Medicine 177(4). p.449-457- Abstract
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management.
OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model.
DESIGN: iStopMM (Iceland Screens, Treats or... (More)
BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management.
OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model.
DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597).
SETTING: Icelandic population of adults aged 40 years or older.
PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample.
MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater.
RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds.
LIMITATION: The prediction model will require external validation.
CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology.
PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.
(Less)
- author
- publishing date
- 2024-04
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adult, Humans, Monoclonal Gammopathy of Undetermined Significance/diagnosis, Multiple Myeloma/diagnosis, Bone Marrow, Cohort Studies, Smoldering Multiple Myeloma, Prospective Studies, Paraproteinemias, Immunoglobulin A, Immunoglobulin G, Disease Progression
- in
- Annals of Internal Medicine
- volume
- 177
- issue
- 4
- pages
- 449 - 457
- publisher
- American College of Physicians
- external identifiers
-
- scopus:85190901683
- pmid:38560901
- ISSN
- 0003-4819
- DOI
- 10.7326/M23-2540
- language
- English
- LU publication?
- no
- id
- 5e0c493e-3072-4c5a-a882-72b17539501e
- date added to LUP
- 2024-12-06 14:47:09
- date last changed
- 2025-06-07 18:39:33
@article{5e0c493e-3072-4c5a-a882-72b17539501e,
abstract = {{<p>BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management.</p><p>OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model.</p><p>DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597).</p><p>SETTING: Icelandic population of adults aged 40 years or older.</p><p>PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample.</p><p>MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater.</p><p>RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds.</p><p>LIMITATION: The prediction model will require external validation.</p><p>CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology.</p><p>PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.</p>}},
author = {{Eythorsson, Elias and Rognvaldsson, Saemundur and Thorsteinsdottir, Sigrun and Einarsson Long, Thorir and Reed, Elin Ruth and Sigurdardottir, Gudrun Asta and Vidarsson, Brynjar and Onundarson, Pall Torfi and Agnarsson, Bjarni A and Sigurdardottir, Margret and Olafsson, Isleifur and Thorsteinsdottir, Ingunn and Sveinsdottir, Signy Vala and Sigurdsson, Fridbjorn and Thordardottir, Asdis Rosa and Palsson, Runolfur and Indridason, Olafur Skuli and Jonsson, Asbjorn and Gislason, Gauti Kjartan and Olafsson, Andri and Sigurdsson, Jon and Steingrimsdottir, Hlif and Hultcrantz, Malin and Durie, Brian G M and Harding, Stephen and Landgren, Ola and Aspelund, Thor and Love, Thorvardur Jon and Kristinsson, Sigurdur Yngvi}},
issn = {{0003-4819}},
keywords = {{Adult; Humans; Monoclonal Gammopathy of Undetermined Significance/diagnosis; Multiple Myeloma/diagnosis; Bone Marrow; Cohort Studies; Smoldering Multiple Myeloma; Prospective Studies; Paraproteinemias; Immunoglobulin A; Immunoglobulin G; Disease Progression}},
language = {{eng}},
number = {{4}},
pages = {{449--457}},
publisher = {{American College of Physicians}},
series = {{Annals of Internal Medicine}},
title = {{Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial}},
url = {{http://dx.doi.org/10.7326/M23-2540}},
doi = {{10.7326/M23-2540}},
volume = {{177}},
year = {{2024}},
}