Why test for kappa light chains?

Testing for Kappa Light Chains in Multiple Myeloma and Related Disorders

Kappa light chain testing is essential for diagnosing, monitoring, and prognosticating multiple myeloma and related plasma cell disorders, with serum free light chain assays providing high sensitivity for detecting monoclonal gammopathies and allowing for quantitative monitoring of disease activity. 1, 2

Diagnostic Purposes

• Serum free light chain (FLC) assay measures levels of free kappa and lambda immunoglobulin light chains, providing critical diagnostic information for plasma cell disorders 3
• Testing for kappa light chains helps establish clonality of plasma cells, which is essential for diagnosing multiple myeloma and related disorders 1
• The combination of serum protein electrophoresis (SPEP) and serum FLC assay detects abnormalities in 99% of patients with amyloidosis, significantly improving diagnostic sensitivity 4
• Kappa/lambda ratio assessment is crucial for identifying abnormal plasma cell populations, as restricted light chain expression becomes apparent when the monoclonal population exceeds 30% of polyclonal cells 1
• Testing is recommended for patients with monoclonal gammopathy of undetermined significance (MGUS) to aid in risk stratification and early detection of progression 1

Monitoring Disease Activity

• Serum FLC measurements are essential for monitoring response to treatment in multiple myeloma, particularly in light chain myeloma and nonsecretory myeloma 2, 5
• The kappa/lambda ratio closely follows clinical disease status, approaching normal range (1.2-9.1) during plateau phase or stable disease, while showing significant deviations during disease progression 6
• In patients with oligosecretory or nonsecretory myeloma, serial FLC measurements can reduce the need for frequent bone marrow biopsies 3
• For patients with light chain amyloidosis, serial FLC measurements outperform protein electrophoresis and immunofixation for monitoring disease 3
• Changes in FLC levels reflect disease activity, making it valuable for early detection of relapse 5

Prognostic Value

• Baseline FLC measurement provides major prognostic value in virtually every plasma cell disorder 3
• The kappa/lambda ratio has prognostic significance, with extreme deviations (19-460 for kappa myeloma and 0.0013-0.14 for lambda myeloma) indicating progressive disease 6
• Abnormal FLC ratios help identify patients with higher risk of progression from precursor conditions like MGUS to active multiple myeloma 2

Technical Considerations

• Serum FLC assay should be performed alongside serum protein electrophoresis and immunofixation for comprehensive evaluation 1
• When monitoring disease, it's crucial to use the same test for serial studies to ensure accurate relative quantification 1
• Serum FLC assay cannot completely replace 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-protein 1, 2
• FLC measurements can be affected by renal function, potentially leading to false elevations 2
• At least 100 neoplastic plasma cell events should be acquired for accurate enumeration when using flow cytometry to assess light chain expression 1

Clinical Applications Beyond Multiple Myeloma

• Testing for kappa light chains is valuable for diagnosing monoclonal gammopathy of renal significance (MGRS), where monoclonal immunoglobulins cause kidney damage 1
• In nonsecretory multiple myeloma, increased concentrations of either kappa or lambda free light chains (and abnormal kappa/lambda ratios) can be detected in approximately 70% of patients, enabling diagnosis and monitoring 5
• Light chain testing helps identify light chain escape, where disease evolves to become oligosecretory, nonsecretory, or light chain-only disease 1

Pitfalls and Caveats

• False-negative rates for lambda chain-associated lesions are higher than for kappa chain-associated lesions, requiring careful interpretation 7
• Urine-free light chain assay should not be performed; instead, 24-hour urine collection for electrophoresis and immunofixation is recommended 1
• A 24-hour urine collection cannot be replaced by a morning urine sample for accurate assessment 1
• Random urine samples with analytes corrected relative to creatinine concentration require further evaluation and cannot be recommended at this point 1