In intact immunoglobulin multiple myeloma:

  • IgG is the most common disease isotype, followed by IgA, IgD, IgM and IgE.
  • An abnormal κ/λ sFLC ratio is detected in around 95% of patients.
  • Monitoring concentration changes in the intact immunoglobulin is essential for assessing patient response.
  • An abnormal IgG or IgA Hevylite® ratio (corresponding to the monoclonal immunoglobulin type) is found in 97 - 100% of both IgG and IgA multiple myeloma patients at diagnosis.
  • Hevylite assays offer an alternative method to densitometric quantification in cases where small monoclonal proteins are obscured by other serum proteins.

Approximately 80% of all multiple myeloma (MM) patients produce monoclonal intact immunoglobulins, with 95% of these also producing monoclonal serum free light chains (sFLCs). IgG intact immunoglobulin multiple myeloma (IIMM) accounts for more than half of all MM patients, and IgA IIMM accounts for a further 20% of cases (Table 17.1) [355]. Only around 1 - 2% of patients have IgD IIMM [356][357] and monoclonal IgM is present in less than 1% of MM patients [356] (more commonly found in Waldenström’s macroglobulinaemia, Chapter 32). IgE MM is extremely rare, with fewer than 50 cases reported in the literature [357]. Around 1-2% of MM patients are diagnosed with biclonal gammopathy (Sections 7.7 and 17.2) [355][1041]. In such cases, two monoclonal proteins are identified that can differ in their heavy chains, light chains or both. It has been proposed that the larger (dominant) monoclonal protein is a product of the active MM clone(s), and the smaller (minor) monoclonal protein represents a separate benign MGUS-like clone (Chapter 13) [1042].

Measurements of the monoclonal intact immunoglobulin and sFLC are essential for diagnosis and follow-up of IIMM, and form the basis of response criteria [113][114][115][116][117][21]. This chapter reviews intact immunoglobulin and sFLC measurements at diagnosis. The limitations of serum electrophoretic techniques used to quantify monoclonal intact immunoglobulins are discussed, along with heavy chain/light chain immunoglobulin (Hevylite, HLC) assays.

Type % of MM patients*
IgGκ 34
IgGλ 18
IgAκ 13
IgAλ 8
IgMκ 0.3
IgMλ 0.2
IgDκ 1
IgDλ 1
κ FLC only 9
λ FLC only 7
Biclonal 2
Negative 7

Table 17.1. Types of serum monoclonal proteins in 1027 patients with multiple myeloma [355]. *Total does not equal 100% due to rounding.