Saudi Society for Clinical Chemistry

Beta Virsion

Multiple Myeloma

Assessing serum biological markers is an essential component of detecting and monitoring multiple myeloma disease progression. Multiple myeloma is the second-most-common blood malignancy and represents approximately 120,000 new cases worldwide per year, writes Joshua Bornhorst, PhD, in the June issue of CLN.


Multiple myeloma is typically characterized by the observation of monoclonal plasma cells, the presence of circulating monoclonal protein immunoglobulin, and related organ damage. Evidence of organ damage resulting from multiple myeloma clonal plasma cell proliferative disorder includes the CRAB criteria of hypercalcemia, renal insufficiency, anemia, and bone lesions.

Improvements in treatment, diagnosis, and monitoring are continually leading to better survival rates, as evidenced by a higher 5-year survival rate of 35% in 2005-2009 versus 10% in the 1970s.

According to the 2014 International Myeloma Working Group (IMWG) guideline on diagnosis of multiple myeloma and smoldering multiple myeloma, the diagnostic criteria for multiple myeloma includes observation of monoclonal plasma cells, monoclonal protein (in most cases) and related organ damage.

The IMWG guidelines also consider the role of circulating protein markers, measured by protein electrophoresis and immunofixation electrophoresis, determination of total serum immunoglobulin concentrations, and serum free light chain (FLC) analysis with derived kappa/lambda ratios.

Other analytes of importance in the workup of suspected or confirmed multiple myeloma include complete blood count, albumin, Beta2 microglobulin, calcium, creatinine, lactate dehydrogenase, total serum protein, liver function tests, C-reactive protein, and vitamin D.

The guidelines define multiple myeloma as >10% clonal bone marrow cells or plasmacytoma, with clinical end organ damage such as CRAB, or the presence of at least one of the following: >60% clonal bone marrow cells; an involved/uninvolved serum FLC ratio >100; or more than one focal lesion in MRI studies. Once diagnosis is established, guidelines for risk stratification in the international staging system use a combination of increasing Beta2 microglobulin concentrations and decreasing albumin measurements to indicate increased risk stratification.

Monoclonal proteins are routinely visualized by serum protein electrophoresis (SPEP) and/or immunofixation electrophoresis (IFE). IFE and SPEP can also be performed on urine to look for the presence of Bence Jones proteins and are often designated as UIFE and UPEP analysis. However, urinalysis protein strips are relatively insensitive to Bence Jones proteins, and absence of elevated urine protein does not exclude multiple myeloma.

Although monoclonal serum FLC can be quantified by SPEP in some cases, the use of a serum FLC nephelometric or turbidimetric polyclonal immunoassay has become standard practice for measuring free kappa (κ) and free lambda (λ) light chains in monoclonal gammopathies and other patient specimens. Alternative monoclonal FLC assays are also becoming available.

Since introduction of the first commercially available serum FLC assay, the clinical value of these tests has been well demonstrated. Most myeloma symptomatic patients (95%) exhibit abnormal κ/λ FLC ratios (FLCr). In addition to their role in diagnosing multiple myeloma and in monitoring disease progression and treatment, serum FLCr also provides information on prognosis for multiple myeloma patients at several points in disease survival.