Prevalence of smoldering multiple myeloma based on nationwide screening

Abstract

Smoldering multiple myeloma (SMM) is an asymptomatic precursor to multiple myeloma. Here we define the epidemiological characteristics of SMM in the general population in Iceland. The iStopMM study (ClinicalTrials.gov ID: NCT03327597 ) is a nationwide screening study for multiple myeloma precursors where all residents in Iceland 40 years or older were invited to participate. SMM was defined as 10-60% bone marrow plasma cells and/or monoclonal (M) protein concentration ≥3 g dl^-1, in the absence of myeloma-defining events. Of the 80,759 who gave informed consent to participate, 75,422 (93%) were screened. The prevalence of SMM in the total population was 0.53% (95% confidence interval (CI) = 0.49-0.57%) in individuals 40 years or older. In men and women, the prevalence of SMM was 0.67% (95% CI = 0.62-0.73%) and 0.39% (95% CI = 0.35-0.43%), respectively; it increased with age in both sexes. For the 193 individuals with SMM, median age was 70 years (range 44-92 years) and 60% were males. The mean M protein concentration of individuals with SMM was 0.62 g dl^-1 (range 0.01-3.5 g dl^-1) and 73% had 11-20% bone marrow plasma cell infiltration. The high prevalence of SMM has implications for future treatment policies in multiple myeloma as the evidence supporting treatment initiation at the SMM stage is emerging.

Fig. 1 |. The iStopMM study design.

All Icelanders >40 years old residing in Iceland on 9 September 2016 (148,704 individuals) were invited to participate. The only exclusion criterion was previously known lymphoproliferative disease other than MGUS or SMM. Participants with abnormal screening tests based on a positive M protein result on SPEP or an abnormal FLC analysis entered an RCT. The RCT was divided into three arms. Participants in arm 1 continued care in the Icelandic healthcare system as though they were never screened. Participants in arms 2 and 3 were evaluated at the study clinic for initial assessment and followup, with participants in arm 2 receiving care according to current guidelines, including bone marrow sampling and skeletal surveys for all except those with low-risk MGUS. In arm 3, bone marrow testing and WBLDCT were offered to all participants. Participants with previously known MGUS were randomized only to arms 2 and 3. Participants with an M protein concentration ≥3.0 g dl⁻¹ or an FLC ratio ≥100 were not randomized but were all called in for evaluation. Participants diagnosed with SMM were enrolled to more intensive follow-up at least every 4 months, with annual bone marrow sampling and WBLDCT. In this article, we report the results from the initial blood and bone marrow screening. The RCT is still ongoing.

Fig. 2 |. Estimated prevalence of SMM by age in the population over 40 years old, using fitted values stratified by sex.

The error bands are the 95% CIs from the fit.