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Prior studies suggest a possible association between autoimmune conditions and monoclonal gammopathy of undetermined significance, but these findings may reflect ascertainment bias inherent in the study design. This current study mitigates the bias by examining the association using data from a population-based screening study. Visual Abstract. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance: Prior studies suggest a possible association between autoimmune conditions and monoclonal gammopathy of undetermined significance, but these findings may reflect ascertainment bias inherent in the study design. This current study mitigates the bias by examining the association using data from a population-based screening study. Background: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor of multiple myeloma (MM) and related conditions. In previous registry-based, retrospective studies, autoimmune diseases have been associated with MGUS. However, these studies were not based on a screened population and are therefore prone to ascertainment bias. Objective: To examine whether MGUS is associated with autoimmune diseases. Design: A cross-sectional study within iStopMM (Iceland Screens, Treats, or Prevents MM), a prospective, population-based screening study of MGUS. Setting: Icelandic population of adults aged 40 years or older. Patients: 75 422 persons screened for MGUS. Measurements: Poisson regression for prevalence ratios (PRs) of MGUS among persons with or without an autoimmune disease, adjusted for age and sex. Results: A total of 10 818 participants had an autoimmune disorder, of whom 599 had MGUS (61 with a prior clinical diagnosis and 538 diagnosed at study screening or evaluation). A diagnosis of an autoimmune disease was not associated with MGUS (PR, 1.05 [95% CI, 0.97 to 1.15]). However, autoimmune disease diagnoses were associated with a prior clinical diagnosis of MGUS (PR, 2.11 [CI, 1.64 to 2.70]). Limitation: Registry data were used to gather information on autoimmune diseases, and the homogeneity of the Icelandic population may limit the generalizability of these results. Conclusion: The study did not find an association between autoimmune disease and MGUS in a systematically screened population. Previous studies not done in systematically screened populations have likely been subject to ascertainment bias. The findings indicate that recommendations to routinely screen patients with autoimmune disease for MGUS may not be warranted. Primary Funding Source: The International Myeloma Foundation and the European Research Council. [ABSTRACT FROM AUTHOR]

Smoldering multiple myeloma is an asymptomatic precursor to multiple myeloma that has a higher risk of progression than monoclonal gammopathy of undetermined significance and may warrant closer monitoring. This study develops a new prediction model to predict the likelihood of smoldering multiple myeloma in persons with monoclonal gammopathy of undetermined significance to inform the decision to obtain a bone marrow sample and compares its performance to the Mayo Clinic risk stratification model. Visual Abstract. Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance: Smoldering multiple myeloma is an asymptomatic precursor to multiple myeloma that has a higher risk of progression than monoclonal gammopathy of undetermined significance and may warrant closer monitoring. This study develops a new prediction model to predict the likelihood of smoldering multiple myeloma in persons with monoclonal gammopathy of undetermined significance to inform the decision to obtain a bone marrow sample and compares its performance to the Mayo Clinic risk stratification model. 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. [ABSTRACT FROM AUTHOR]

There is some evidence that a prior cancer is a risk factor for the development of multiple myeloma (MM). If this is true, prior cancer should be associated with a higher prevalence or increased progression rate of monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM and related disorders. Those with a history of cancer might therefore constitute a target population for MGUS screening. This two-part study is the first study to evaluate a relationship between MGUS and prior cancers. First, we evaluated whether prior cancers were associated with having MGUS at the time of screening in the Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM) study that includes 75,422 individuals screened for MGUS. Next, we evaluated the association of prior cancer and the progression of MGUS to MM and related disorders in a population-based cohort of 13,790 Swedish individuals with MGUS. A history of prior cancer was associated with a modest increase in the risk of MGUS (odds ratio=1.10; 95% confidence interval: 1.00-1.20). This excess risk was limited to prior cancers in the year preceding MGUS screening. A history of prior cancer was associated with progression of MGUS, except for myeloid malignancies which were associated with a lower risk of progression (hazard ratio=0.37; 95% confidence interval: 0.16-0.89; P=0.028). Our findings indicate that a prior cancer is not a significant etiological factor in plasma cell disorders. The findings do not warrant MGUS screening or different management of MGUS in those with a prior cancer.