Several screening studies have assessed the prevalence of monoclonal gammopathy of undetermined significance (MGUS), reporting varying incidences from 2.4 to 4% in the general population over the age of 50 years. The prevalence of smoldering multiple myeloma (SMM) has, however, never been assessed or reported, likely because it requires thorough patient assessment with laboratory tests, bone marrow biopsy, and imaging. Additionally, SMM is not included in the International Classification of Disease, Tenth Revision (ICD-10) disease classifying system as its own diagnosis, which hampers registry-based SMM studies. For a diagnosis of SMM, individuals should have bone marrow plasma cell infiltration between 10% and 59% and/or an M spike value >3 g/dL. They should not fulfill the criteria for myeloma-defining events, such as CRAB and biomarker criteria.1
Recently, the Icelandic group behind the iStopMM (Iceland screens, treats, or prevents multiple myeloma) trial published the first-ever study on prevalence of SMM. The iStopMM program is a large nationwide screening study for myeloma precursor disease.2 All Icelanders over the age of 40 years were invited to enroll in the trial; more than 80,000 people consented and 75,422 individuals were enrolled and screened. Initial screening was done through serum electrophoresis, immunofixation, and free light chain assays. Confirmatory workup with bone marrow biopsies were done in all individuals with SMM in this study.
Dr. Sigrún Thorsteinsdóttir and colleagues found that the overall SMM prevalence was 0.53% (95% CI, 0.49-0.57) in individuals 40 years or older.3 The prevalence was higher in men than women (0.67% [95% CI, 0.62-0.73] versus 0.39% [95% CI 0.35-0.43]) and was higher in the older age groups. The median age of individuals with SMM was 70 years. The mean M spike level was 0.62 g/dL and 73% of patients had bone marrow plasma cell infiltration between 11 and 20%. Using the 2/20/20 risk stratification method, most patients were considered to have low-risk SMM.4
In Brief
The iStopMM trial is truly an impressive effort that will inform the biology and mechanisms of plasma cell disease progression for years to come. One caveat to the trial is the homogenous population in Iceland, which is largely Caucasian. As a comparison, U.S. screening studies on MGUS have reported a two-fold higher prevalence in African Americans but a lower prevalence in Hispanic populations.5 On the other hand, this observed difference may be related to socioeconomic factors, which would play a smaller role in the Icelandic population. Individuals’ willingness to participate, along with the nationwide health coverage and health registries in Iceland, made this trial feasible. Through the prospective iStopMM trial, the Icelandic group will continue to answer questions regarding risk profiles and driver mechanisms in MGUS and SMM, as well as the value of early treatment for SMM.
Competing Interests
Dr. Hultcrantz and Dr. Usmani indicated no relevant conflicts of interest.
