From the Guidelines
Increased lambda and kappa free light chains (FLCs) are indicative of plasma cell disorders, most commonly multiple myeloma, but also other conditions like monoclonal gammopathy of undetermined significance (MGUS), amyloidosis, and certain lymphoproliferative disorders. When both lambda and kappa FLCs are elevated together, this typically suggests polyclonal B-cell activation rather than a monoclonal process, which can occur in inflammatory conditions, infections, autoimmune diseases, or renal impairment. The kappa/lambda ratio is crucial for interpretation - a normal ratio (0.26-1.65) with elevated absolute values often indicates kidney disease or inflammation, while an abnormal ratio suggests a monoclonal process.
- Key points to consider:
- Serum FLC testing is particularly valuable for diagnosing and monitoring light chain myeloma, amyloidosis, and nonsecretory myeloma.
- The degree of elevation can correlate with disease burden, making FLC measurements useful for monitoring response to therapy.
- Renal function should always be considered when interpreting FLC results, as impaired kidney function can cause retention of both light chains without indicating a plasma cell disorder.
- The International Myeloma Working Group (IMWG) diagnostic criteria for MM require 10% or more clonal plasma cells in the bone marrow (and/or a biopsy proven plasmacytoma) plus any one or more myeloma defining events (MDE) 1.
- The serum FLC assay also has prognostic value in plasma cell disorders, including monoclonal gammopathy of undetermined significance, smoldering myeloma, active myeloma, immunoglobulin light chain amyloidosis, and solitary plasmacytoma 1.
- The FLC ratio is required for documenting stringent complete response according to the International Myeloma Working Group (IMWG) Uniform Response Criteria 1.
- The most recent guidelines from 2020, emphasize the importance of serum FLC assay in the diagnosis and monitoring of multiple myeloma 1.
From the Research
Increased Lambda and Kappa FLC Indicative Of
- Increased lambda and kappa free light chains (FLC) are indicative of multiple myeloma and other plasma cell disorders 2, 3, 4
- An abnormal kappa/lambda ratio, either high or low, is associated with poorer survival in patients with multiple myeloma 2
- Elevated levels of either kappa or lambda FLC can be detected in patients with nonsecretory multiple myeloma, making FLC measurements useful for diagnosis and monitoring 3
- The kappa/lambda ratio may be genetically linked, with twin siblings showing similar ratios 5
- Serial FLC measurements can be used to monitor patients with oligosecretory plasma cell disorders, including light chain amyloidosis and oligosecretory myeloma 4
- The concentrations of involved and uninvolved serum free light chains can be used to assess the severity of light-chain myelomas, with comparable levels of involved light chains in kappa-chain and lambda-chain myelomas 6