Serum Free Light Chain Assays for the Diagnosis and Monitoring of Multiple Myeloma and Other Monoclonal Gammopathies

October 31, 2006: Karen van Hoeven, MD

The serum free kappa and lambda light chain assays provide a highly sensitive tool for the diagnosis and monitoring of patients with monoclonal gammopathies. An abnormal kappa:lambda ratio supports the presence of clonal plasma cell expansion and requires further investigation. More than 95% of patients with myeloma, > 99% of light chain myeloma, > 95% of AL amyloidosis, and a majority of patients with light chain deposition disease are detectable with this technology. Importantly, many patients with “nonsecretory” myeloma have been reclassified with “oligosecretory” myeloma because of the sensitivity of the free light chain assays in identifying M-proteins.

Serum protein electrophoresis detects paraproteins in approximately 80% of patients with multiple myeloma. A panel of serum free light chain testing combined with serum protein electrophoresis provides > 99% accuracy in the front-line diagnosis of monoclonal gammopathies and eliminates the need for urine testing in most instances.

The half-life of free light chains is less than 6 hours compared with 20–25 days for IgG. Thus, free light chain measurements at short sampling intervals provide a rapid, real-time assessment of treatment-induced tumor kill, dose adequacy, and possible need for alternative chemotherapeutic approaches. Normalization of the involved free light chain concentration after treatment has been shown to have prognostic significance in AL amyloidosis.

Quantification of free kappa and free lambda light chains is an automated latex-enhanced immunoassay available on various nephelometric and turbidimetric platforms. Its high sensitivity and specificity provides the clinical chemist with a valuable tool in the diagnostic evaluation of monoclonal gammopathies, and these assays have the potential to replace urine testing in this setting.

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