Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed- and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM) were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay. We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio: 2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.

Monoclonal Gammopathies and CKD Progression

“…4,5,10 Patients were likely identified to have MGUS during workup of other conditions, including CKD and heart failure, a phenomenon recently described by Sigurbergsdóttir et al in a large screening study in Iceland. 10…”

“…4,5,10 Patients were likely identified to have MGUS during workup of other conditions, including CKD and heart failure, a phenomenon recently described by Sigurbergsdóttir et al in a large screening study in Iceland. 10 In addition, there is some question of how CKD was defined. Patients were first identified as having CKD on the basis of International Classification of Diseases codes, which are specific but insensitive for diagnosing CKD.…”

“…This is substantially higher than the proportion of patients with MGUS in other studies, which reported that 11.6%, 9.6%, and 4.4% had MGUS, respectively. 4,5,10 Patients were likely identified to have MGUS during workup of other conditions, including CKD and heart failure, a phenomenon recently described by Sigurbergsdóttir et al in a large screening study in Iceland. 10 In addition, there is some question of how CKD was defined.…”