Annals of Internal MedicineDevelopment 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

In an effort to refine clinical decision-making for individuals with Monoclonal Gammopathy of Undetermined Significance (MGUS), researchers have developed a multivariable prediction model aimed at determining the necessity for bone marrow sampling. This model, tested within a cohort study nested in a clinical trial, provides a systematic approach to assessing the probability of a patient with presumed MGUS having a significant percentage of bone marrow plasma cells, thereby indicating a potential progression to smoldering multiple myeloma (SMM) or worse conditions.

Key Points:

• The study aimed to create a model that predicts the likelihood of patients with presumed MGUS having ≥10% bone marrow plasma cells, a criterion for diagnosing SMM or more severe conditions.
• Conducted within the iStopMM trial in Iceland, this study involved a population-based screening of 1,043 individuals with various types of MGUS.
• Key variables in the predictive model included MGUS isotype, monoclonal protein concentration, free light-chain ratio, and total concentrations of IgG, IgM, and IgA.
• The model demonstrated a high c-statistic of 0.85, indicating strong predictive accuracy, with excellent calibration metrics (intercept -0.07; slope 0.95).
• At a 10% predicted risk threshold for SMM or worse, the model achieved 86% sensitivity and 67% specificity, with a 32% positive predictive value and a 96% negative predictive value.
• The model outperformed the Mayo Clinic risk stratification model, offering higher net benefits for bone marrow sampling decisions across various risk thresholds.
• Limitations acknowledged include the necessity for external validation of the prediction model before widespread clinical application.

MGUS is the most common plasma cell dyscrasia and is prevalent in approximately 3% of the general population 50 years of age and older. The prevalence increases with age; the incidence has been reported as 1.7% in those 50 to 59 years of age and as over 5% in those older than the age of 70.

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