Multiple myeloma (MM) is a clonal bone marrow disorder of plasma cells. MM is preceded by the precursor conditions monoclonal gammopathy of undetermined significance (MGUS) and smouldering myeloma (SMM). SMM sits between MGUS and MM, representing a plasma cell clone (10%–59%) without organ or tissue impairment. In retrospective data, prior to the updated IMWG criteria, the risk of SMM progressing to MM or a related disorder is 10% per year for the first 5 years after diagnosis, 3% per year for the next 5 years and 1% per year for the next 10 years1 with biological behaviour ranging from MGUS to high-risk MM.2 The time of diagnosis is, however, random given that it is an asymptomatic condition, and therefore, most patients will have had SMM for some unknown time before diagnosis. Similar genetic changes are detected in MGUS, SMM and MM and include hyperdiploidy (typically trisomies of odd chromosomes 3, 5, 7, 9, 11, 15, 19, 21) or translocations involving the immunoglobulin loci (common translocation partners: MMSET/FGFR3, CCND1, CCND3, MAF, MAFB1).3-6 Copy number alterations (commonly del(13q), gain(1q), del(14q), del(1p), del(17p))6 and single nucleotide variants (SNVs) generally increase with progression to MM but the genomic makeup of the myeloma clone is nearly fully acquired by the time of SMM diagnosis in the majority of cases.5, 7 In keeping with the random timepoint of SMM diagnosis, using mutational signatures to reconstruct chronological development of these genetic abnormalities, some initiating translocations leading to transformation of post-germinal centre B cells may occur in the second or third decade of life.8
Declaration of Interests
The BSH paid the expenses incurred during the writing of this guidance. None of the authors had conflicts of interest to declare. All authors have made a declaration of interests to the BSH and Task Force Chairs which may be viewed on request.