Chapter 14

In smouldering multiple myeloma:

  • sFLCs are abnormal in approximately 80% of patients.
  • Abnormal κ/λ sFLC ratios are associated with an increased risk of progression.
  • Asymptomatic patients with an involved/uninvolved sFLC ratio ≥100 and 10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma have been reclassified as multiple myeloma requiring treamtent.

Smouldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder. In 2014, the International Myeloma Working Group (IMWG) revised their definition of SMM [42]. 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) [42]. 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. [916], 13% of SMM patients were re-classified as MM using this definition. Similar findings were reported by Kyrtsonis et al. [290].

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 [255][292][293][294]. 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).