Findings from the iStopMM study, a nationwide screening study in Iceland, showed that the prevalence of smoldering multiple myeloma (SMM) is 0.53% in individuals ages 40 and older, with more than a third of patients having either intermediate- or high-risk disease. Study findings were published in Nature Medicine.
According to the researchers, led by Sigrún Thorsteinsdóttir, MD, of the University of Iceland in Reykjavík, the study “is of public health relevance,” given the global debate regarding when to initiate therapy in multiple myeloma (MM). “Our results show that screening could identify possible candidates for early treatment,” the researchers wrote.
The iStopMM study invited residents of Iceland ages 40 years and older to participate in a nationwide screening study for MM precursors. Individuals who participated in the study underwent serum protein electrophoresis and free light chain (FLC) testing.
To identify SMM, the investigators defined the disease as the presence of 10% to 60% bone marrow plasma cells or a monoclonal (M) protein concentration of at least 3 g/dL in the absence of myeloma-defining events.
Of the 148,704 individuals in Iceland over the age of 40, the 75,422 (51%) who provided informed consent for participation were screened for abnormal M protein concentration and serum-derived FLC ratio.
Among all screened participants, the median age was 61 years (range = 41-103). Approximately 46% were male and 54% were female. Abnormal screening results were observed in 3,704 participants who were then randomly assigned to one of three arms that consisted of different follow-up strategies.
In arm 1 (n=1,162), patients did not undergo further work-up. In arm 2 (n=1,272), patients received guideline-based management, with 525 patients undergoing bone marrow sampling. Arm 3 (n=1,270) consisted of patients who underwent intensive follow-up with bone marrow testing and whole-body, low-dose computed tomography.
Overall, 193 individuals – 60% male and 40% female – were diagnosed with SMM. The median age of this cohort was 70 years. Most of these patients (92%) had a detectable M protein at the time of SMM diagnosis, with a mean M protein concentration of 0.62 g/dL (range = 0.01-3.5 g/dL). Similar characteristics were reported in the 112 patients with SMM in arm 3.
In the total population, the prevalence of SMM was 0.53%. Across sexes, the prevalence was 0.67% in men and 0.39% in women, but these rates increased with age in both groups.
The risk of being diagnosed with SMM did not increase with age and was not significantly different between sexes in the patients assigned to arm 3 who had a positive screening for M protein or FLC analysis.
Applying the proposed 2/20/20 clinical risk stratification model for SMM, the investigators identified 65% of patients with low-risk disease, 27% of patients with intermediate-risk disease, and 8% of patients with high-risk disease.
A limitation of the iStopMM study was the inclusion of only the Icelandic population, which the researchers indicated is genetically homogenous and nearly exclusively white. Given this limitation, the researchers explained that the findings may not be generalizable across other populations since the epidemiology of monoclonal gammopathy of undetermined significance and MM are associated with race and ethnicity.
Furthermore, the researchers noted the final results of the iStopMM study are needed to gain a deeper understanding of survival and quality of life, while more optimal “biology-oriented strategies” are also needed to better define an individual patient’s risk of progression.
“Such efforts will allow clinicians to focus their care on those who benefit the most from surveillance and therapeutic interventions, preventing overtreatment and enabling early detection and early effective treatments, improving outcomes in individuals with SMM and [MM] worldwide,” the researchers wrote.
Any conflicts of interest declared by the authors can be found in the original article.
Thorsteinsdóttir S, Gíslason GK, Aspelund T, et al. Prevalence of smoldering multiple myeloma based on nationwide screening. Nat Med. 2023;29(2):467-472.