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Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal
Elias Eythorsson1, Saemundur Rognvaldsson1, Sigrun Thorsteinsdottir2
1Landspítali-The National University Hospital of Iceland and Faculty of Medicine, University of Iceland, Reykjavík, Iceland (E.E., S.R., P.T.O., B.A.A., R.P., O.S.I., S.Y.K.).
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.
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