Multiple myeloma (MM) is an incurable and debilitating cancer of cells of the immune system located in the bone marrow called plasma cells. MM develops over years from a precursor condition, monoclonal gammopathy of undetermined significance (MGUS) at a rate of 1-2% per year. MGUS is common in the general population, with 4-5% of individuals over 50 years old. Current guidelines recommend indefinite follow-up of individuals with MGUS but there are no prospective studies to guide this follow-up. Recently there have been indications that treating MM at a precursor state, at the more advanced state of smoldering MM (SMM), improves outcomes, including overall survival. Individuals with previous knowledge of MGUS, i.e. were under surveillance for MM, had a superior survival when diagnosed with MM. These findings indicate that early treatment in MM leads to better outcomes in this deadly and debilitating disease. However, MGUS and SMM are asymptomatic and are currently always diagnosed incidentally during work-up for other medical problems limiting the availability of early treatment in MM. This project aims to close this gap of detection by population wide screening for MM and its precursors and performing a randomized trial, including early treatment, to evaluate the potential benefits and harms of screening. Importantly, this includes assessing the psychological effects of MGUS diagnosis (quality of life, anxiety, psychological trauma) and developing optimal follow-up strategies. Furthermore, since most individuals with precursors of MM do not progress and will remain asymptomatic, this includes integrating clinical, biological, imaging, and germline genetic markers to create a comprehensive risk assessment tool to evaluate individual risk of progression from precursor to active disease. Additionally, data from the study will be cross linked to accurate and complete government registries on cancers, prescription medications, and causes of death as well as all medical records in Iceland, including laboratory testing. This data provides unprecedented completeness of relevant medical data. Furthermore, blood, bone marrow, and urine samples provided regularly will be stored in a biobank for future studies.
By early detection and early treatment of MM at a precursor state, we believe MM can move from an incurable and debilitating disease, to a manageable, if not curable, disorder. In addition to this paradigm shift in MM management the study will also provide evidence for optimal diagnostics and follow-up in MGUS, as well as improved risk stratification. Also, by including extensive epidemiologic and biologic data and by collecting samples into a large biobank, the study will be able to greatly improve our understanding of the biology underlying MM development. Furthermore, by conducting a population-based screening study including a focus on the psychological effects of cancer screening, the project will also impact screening programs for other cancers and may create a new „gold-standard“ for conducting cancer screening trials.
