Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

The Current Role of the Heavy/Light Chain Assay in the Diagnosis, Prognosis and Monitoring of Multiple Myeloma: An Evidence-Based Approach

“…Moreover, a higher association of IMI rather than classical immunoparesis with progression is reported. Likely, the iStopMM study (NCT03327597), conducting a population-based screening for MGUS in more than 80,000 participants [57], will help to definitively define the role of the HLC assay in this patient population. In SMM, only one prospective study has been reported as suggesting a higher correlation of the risk of progression with IMI than with classical immunoparesis [49].…”

Monoclonal gammopathy of undetermined significance and COVID-19: a population-based cohort study

“…Serum samples were collected from 75,422 study participants (93%) between September 9, 2016 and December 31 2020 and screened for MGUS by capillary zone electrophoresis (CZE), immunofixation electrophoresis (IFE), and serum FLC assay. The iStopMM study design has previously been described in detail [ 24 ].…”

MicroRNAs as a Potential New Preventive Approach in the Transition from Asymptomatic to Symptomatic Multiple Myeloma Disease

“…However, at the present, available results are still too preliminary to achieve statistical significance. Nevertheless, two paradigmatic examples aiming to deep-screen and prevent MM by collecting high-throughput data are represented by the researches performed by Pichiorri et al [37] and within the iStopMM initiative (NCT03327597; NCT03815279) [106]. This last approach, taking advantage of a genetic screening in a population-based nationwide clinical trial with early intervention, offers the potential to collect a large biobanking repository available for future biological studies, including epigenetic profiling.…”