Smouldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder. In 2014, the International Myeloma Working Group (IMWG) revised their definition of SMM . A definitive diagnosis requires two criteria to be met: 1) the presence of a serum monoclonal protein (IgG or IgA) at a concentration of ≥30 g/L or a urinary monoclonal protein ≥500 mg/24 hours and/or 10 - 60% clonal bone marrow plasma cells (BMPCs), and 2) the absence of myeloma defining events or amyloidosis (Section 25.2) . The revised definition of SMM excludes asymptomatic patients with clonal BMPCs ≥60%, an involved/uninvolved sFLC ratio of ≥100, or those with two or more focal lesions revealed by MRI, which in conjunction with a minimum of 10% clonal BMPC or biopsy-proven plasmacytoma are consistent with a diagnosis of multiple myeloma (MM, Section 25.2). In a retrospective audit of 216 SMM patients by Kastritis et al. , 13% of SMM patients were re-classified as MM using this definition. Similar findings were reported by Kyrtsonis et al. .
Risk stratification is valuable for SMM patient management. Patients identified as high-risk require close follow-up and, if possible, inclusion into clinical trials. Early studies identified a variety of risk factors for progression, including a high percentage of BMPCs, a monoclonal protein concentration ≥30 g/L, an IgA isotype and Bence Jones proteinuria . Subsequently, monoclonal serum free light chains (sFLCs) were identified as a significant, independent risk factor, as discussed below. Preliminary evidence suggests that immunoglobulin heavy/light chain (Hevylite®, HLC) assays may also have a role in SMM prognosis (Section 14.4).