| Summary: | Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic disorder caused by the accumulation of monoclonal immunoglobulin secreting cells in the bone marrow. The main clinical implication of MGUS is that it’s the precursor of multiple myeloma (MM) and related disorders. Current guidelines recommend indefinite follow-up of individuals with MGUS in order to detect MGUS progression. The benefits of this follow-up and of detecting MGUS have not been sufficiently studied but recent evidence has suggested that the detection of MGUS provides opportunities of early treatment in MM and related disorder at an asymptomatic stage and that such early treatment can significantly improve outcomes. Systematic screening may provide a means to vastly expand the availability of early treatment but has not been sufficiently studied. MGUS may also have other clinical significance with multiple studies associating the asymptomatic disorder with a wide range of non-malignant disorders. However, previous studies have been heavily afflicted by bias and the extent of these associations and their clinical relevance is not clear. The aim of this thesis is to further clarify the clinical significance of MGUS with an emphasis on the association of MGUS and non-malignant disease and to demonstrate methodologies that can significantly improve our understanding of this asymptomatic precursor disorder and its clinical significance. Four papers are presented. The first two papers apply alternative study designs and statistical methods to registry-based data on MGUS from Sweden to study the relationship between MGUS and peripheral neuropathy (PN) and fractures. The latter two papers pertain to the Iceland screens, treats, or prevents multiple myeloma study (iStopMM), a population-based screening study with the aim of gathering a population- based cohort of individuals screened for MGUS and to assess the benefits and harms of such screening in a clinical trial. The study is described in detail in paper three and the fourth paper ...
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