TY - JOUR
T1 - Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance
T2 - A Cohort Study Nested in a Clinical Trial
AU - Eythorsson, Elias
AU - Rognvaldsson, Saemundur
AU - Thorsteinsdottir, Sigrun
AU - Einarsson Long, Thorir
AU - Reed, Elin Ruth
AU - Sigurdardottir, Gudrun Asta
AU - Vidarsson, Brynjar
AU - Onundarson, Pall Torfi
AU - Agnarsson, Bjarni A
AU - Sigurdardottir, Margret
AU - Olafsson, Isleifur
AU - Thorsteinsdottir, Ingunn
AU - Sveinsdottir, Signy Vala
AU - Sigurdsson, Fridbjorn
AU - Thordardottir, Asdis Rosa
AU - Palsson, Runolfur
AU - Indridason, Olafur Skuli
AU - Jonsson, Asbjorn
AU - Gislason, Gauti Kjartan
AU - Olafsson, Andri
AU - Sigurdsson, Jon
AU - Steingrimsdottir, Hlif
AU - Hultcrantz, Malin
AU - Durie, Brian G M
AU - Harding, Stephen
AU - Landgren, Ola
AU - Aspelund, Thor
AU - Love, Thorvardur Jon
AU - Kristinsson, Sigurdur Yngvi
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - Adult
KW - Bone Marrow
KW - Cohort Studies
KW - Disease Progression
KW - Humans
KW - Immunoglobulin A
KW - Immunoglobulin G
KW - Monoclonal Gammopathy of Undetermined Significance/diagnosis
KW - Multiple Myeloma/diagnosis
KW - Paraproteinemias
KW - Prospective Studies
KW - Smoldering Multiple Myeloma
UR - http://www.scopus.com/inward/record.url?scp=85190901683&partnerID=8YFLogxK
U2 - 10.7326/M23-2540
DO - 10.7326/M23-2540
M3 - Journal article
C2 - 38560901
SN - 0003-4819
VL - 177
SP - 449
EP - 457
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 4
ER -