Monoclonal gammopaty of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursors of multiple myeloma (MM). Emerging data from clinical trials indicate that initiation of treatment at the stage of high-risk SMM can improve outcomes in MM. Currently there is no established screening for MM precursors and most MM patients are therefore diagnosed after the development of symptomatic end-organ damage. The Iceland screens, treats, or prevents multiple myeloma (iStopMM) study (ClinicalTrials.gov #NCT03327597) is a nationwide screening study investigating the benefits and harms of screening for MM precursor conditions. All individuals residing in Iceland over 40 years of age (n = 148,711) were offered participation with 75,422 (51%) were screened using serum protein electrophoresis (SPEP) and free light chain (FLC) analysis. The 3,725 with abnormal screening were randomized to one of the three arms of the study, and bone marrow sampling was performed in over 1,600 individuals.
The iStopMM study started in 2016 and is still ongoing. First results from the screening show that the prevalence of MGUS is 4.5% and the prevalence of SMM is 0.5% in individuals over 40 years old, both conditions are more common in men than women and the prevalence increases with age. Around one third of the SMM patients have intermediate- to high-risk SMM according to the Mayo Clinic 20/2/20 risk stratification model, and could potentially be candidates for early treatment. Furthermore, initial results from the randomized clinical trial show that active screening identified significantly higher number of individuals with full-blown malignancy (MM and related disorders) than in the control arm. These first results show that screening is feasible, however, until the final results from the iStopMM study become available, including overall survival data, data on MM related organ damage and quality of life, we advise against systematic MGUS screening in healthy individuals.