What is the significance of elevated lambda (λ) light chains and kappa (κ) light chains?

From the Guidelines

Elevations in lambda and kappa light chains are significant indicators of potential plasma cell disorders, and a comprehensive workup including serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain assay is essential for evaluation. When both light chains are elevated, this often suggests a polyclonal gammopathy rather than a monoclonal process, with common causes including inflammatory conditions, chronic infections, liver disease, or renal impairment where decreased clearance leads to accumulation of both light chains 1.

Key Considerations

• The most recent and highest quality study, published in 2017, emphasizes the importance of serum free light chain (FLC) assay in the initial diagnostic workup for multiple myeloma and related plasma cell disorders 1.
• The FLC ratio is crucial for documenting stringent complete response according to the International Myeloma Working Group Uniform Response Criteria, and an abnormal ratio can indicate the presence of an abnormal clone 1.
• Additional testing, such as complete blood count, comprehensive metabolic panel, and assessment of kidney function, is necessary since light chains can cause renal damage 1.
• If clinical suspicion for a plasma cell disorder remains high, bone marrow biopsy may be necessary to confirm the diagnosis and guide treatment decisions 1.

Diagnostic Approach

• A complete workup should include SPEP, IFE, and serum free light chain assay with attention to the kappa/lambda ratio.
• Normal ratios (0.26-1.65) despite elevations suggest polyclonal processes, while abnormal ratios indicate potential monoclonal disorders like multiple myeloma or other plasma cell dyscrasias.
• The FLC assay cannot replace the 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-proteins 1.

Treatment Implications

• Treatment depends on the underlying cause rather than targeting the light chain elevations directly.
• The presence of certain chromosomal abnormalities, such as deletion of 17p13 or t(4;14), can impact prognosis and treatment decisions 1.
• Participation in clinical trials is especially encouraged, as the best management for any cancer patient is often in a clinical trial 1.

From the Research

Significance of Elevated Lambda (λ) and Kappa (κ) Light Chains

• Elevated lambda (λ) and kappa (κ) light chains are significant in the diagnosis and monitoring of multiple myeloma and other plasma cell disorders 2, 3, 4, 5, 6
• The ratio of kappa to lambda light chains can be used to diagnose and monitor multiple myeloma, with an abnormal ratio indicating the presence of a plasma cell disorder 3, 4
• Elevated free light chains can be monoclonal or polyclonal, and are associated with an inferior survival in patients with non-Hodgkin lymphoma 5
• The concentration of serum free light chains is useful in the evaluation of monoclonal gammopathic manifestations, but has a high false-positive and false-negative rate 6

Clinical Implications

• Elevated lambda (λ) and kappa (κ) light chains can indicate the presence of a plasma cell disorder, such as multiple myeloma or light-chain myeloma 2, 4, 6
• The measurement of kappa/lambda ratio is more sensitive than serum protein electrophoresis and immunofixation in monitoring the disease course of multiple myeloma 4
• Elevated free light chains are associated with an inferior event-free survival and overall survival in patients with non-Hodgkin lymphoma 5

Diagnostic Challenges

• The diagnosis of light-chain multiple myeloma can be challenging due to the absence of a visible M-spike in serum protein electrophoresis 2
• The false-negative rate for lambda chain-associated lesions is higher than that for kappa chain-associated lesions, making diagnosis more challenging 6