Chapter 13


  • Intact immunoglobulin monoclonal gammopathy of undetermined significance (MGUS) accounts for 80% of all MGUS cases, of which approximately one-third have an abnormal sFLC ratio.
  • Light chain MGUS accounts for approximately 20% of all MGUS cases and is characterised by an abnormal sFLC ratio and an elevated concentration of the involved FLC.
  • sFLCs have been incorporated into an MGUS risk-stratification model, in association with the monoclonal immunoglobulin class and concentration, to guide patient management.
  • Hevylite® pair suppression is an independent risk factor for progression and improves the standard risk stratification model.

Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal protein in the serum of asymptomatic individuals who do not meet the diagnostic criteria for multiple myeloma (MM), AL amyloidosis, Waldenström's macroglobulinaemia (WM), lymphoproliferative disorders, plasmacytoma or related conditions. Whilst most MGUS patients have a stable condition and remain asymptomatic, a small proportion will progress to MM or a related B-cell or lymphoid cancer. This equates to a 1%-per-year lifelong risk of malignant transformation [249].

MGUS is defined as follows (all criteria must be met): 1) a serum monoclonal protein <30 g/L; 2) clonal bone marrow plasma cells <10%; and 3) the absence of end-organ damage such as hypercalcaemia, renal insufficiency, anaemia, and bone lesions that can be attributed to the plasma cell proliferative disorder. The definition of MGUS should not be confused with the term “monoclonal gammopathy of renal significance” (MGRS), which is used to describe a group of haematological disorders associated with kidney disease that fail to meet the standard definitions for MM or lymphoma (Chapter 26) [262].

MGUS is present in approximately 3% of individuals aged 50 or older, and in around 5% of those aged 70 or older [10]; it has a 2-fold higher incidence in African-Americans [263] and is more common in individuals with autoimmune, infectious and inflammatory disorders [264]. Due to the high frequency of MGUS, it typically accounts for between 50 and 65% of all monoclonal proteins detected, although around 80% of individuals will be unaware that they have the condition [265].

Historically, the term MGUS was used only to describe patients with a monoclonal intact immunoglobulin. In a Mayo Clinic study, 70% of monoclonal proteins identified were IgG, 15% IgM, 12% IgA and 3% biclonal [249]. In addition, the term “idiopathic Bence Jones proteinuria” was used to describe the presence of a monoclonal light chain in the urine (>200 mg/24-hour), in the absence of both an intact immunoglobulin monoclonal protein in the serum and end-organ damage attributable to a plasma cell proliferative disorder. Such patients are at high risk for the development of MM or AL amyloidosis, with a cumulative probability of progression of 20% at 5 years [266]. In 2010 a new category termed light chain MGUS was recognised, and this represents the pre-malignant precursor of light chain MM (LCMM) (Section 13.3.2) [267].