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Chapter 16

In nonsecretory multiple myeloma, sFLC measurements:

  • Are abnormal in the majority of patients and are important for diagnosis.
  • Can be used for monitoring, without the need for frequent bone marrow biopsies or radiological scans.
  • Are recommended by international guidelines for diagnosis and monitoring.
  • Allow patients to be included in clinical trials from which they were previously excluded.

Nonsecretory multiple myeloma (NSMM) accounts for 1 - 5% of all multiple myeloma (MM) cases [15][337]. The disease is characterised by the absence of detectable monoclonal proteins in serum and urine using immunofixation electrophoresis (IFE) [15][338][339]. However, monoclonal proteins can usually be detected immunohistochemically in bone marrow plasma cells (BMPCs) indicating that the patients have tumour cells that produce but may not secrete monoclonal immunoglobulins into the blood. Also, using highly sensitive tests such as isoelectric focusing, monoclonal proteins have been detected in the sera of some patients [340]. Ultimately, only 10 - 15% of NSMM patients are true “non-producers” in whom tumour plasma cells contain no detectable immunoglobulins [341].

As electrophoresis procedures for detecting monoclonal proteins have become more sensitive and reliable, fewer patients are now diagnosed with NSMM. Yet, even in expert hands, 2 - 3% of patients with MM have undetectable serum or urine monoclonal proteins by IFE and are classified as NSMM [338][342][343][321]. From a logical standpoint, such patients cannot be producing significant amounts of intact monoclonal immunoglobulins; IgG molecules accumulate in serum with a half-life of 3 - 4 weeks, so their production from even small clones of plasma cells can be visualised as monoclonal bands on serum protein electrophoresis (SPE) gels. By contrast, free light chains (FLCs) have a serum half-life of only 2 - 6 hours, 100- to 200-fold less (Section 3.5). Clonal production of monoclonal FLCs, therefore, needs to be correspondingly much greater to produce similar serum concentrations of monoclonal protein to those found in IgG-producing MM. NSMM patients are therefore more likely to be producing low amounts of monoclonal FLC. Urinalysis may also be unhelpful because patients with NSMM usually have normal renal function. The modest monoclonal FLC production, typically seen, may not be sufficient to damage or overwhelm the reabsorption capacity of the kidneys and enter the urine (Section 3.5.2). Hence, more sensitive methodologies are required when the production of FLCs is too low for detection by electrophoresis techniques.