What is the significance of the Kappa (kappa):Lambda (lambda) ratio in immunoglobulin testing?

From the Guidelines

The Kappa:Lambda ratio is a crucial diagnostic tool for evaluating monoclonal gammopathies, with a normal reference range between 0.26-1.65, and an abnormal ratio suggests the presence of a monoclonal protein, which may indicate conditions like multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), or other plasma cell disorders, as stated in the 2019 study by the American Society of Clinical Oncology (ASCO) and the Canadian Cancer Organization (CCO) 1.

Key Points to Consider

• The Kappa:Lambda ratio is used to evaluate for monoclonal gammopathies, with a normal range between 0.26-1.65.
• An abnormal ratio (either elevated or decreased) suggests the presence of a monoclonal protein.
• When interpreting this ratio, consider both the absolute values of kappa and lambda light chains as well as the ratio itself.
• A significantly abnormal ratio combined with elevated free light chains is more concerning than a mildly abnormal ratio with normal absolute values.

Diagnostic Criteria

• The International Myeloma Working Group (IMWG) Uniform Response Criteria define a stringent complete response (sCR) as a normal free light chain (FLC) ratio and absence of clonal cells in bone marrow, in addition to other criteria 1.
• The IMWG criteria also define complete response (CR), very good partial response (VGPR), partial response (PR), and stable disease (SD) based on serum and urine M-protein levels, FLC levels, and other factors.

Clinical Implications

• An abnormal Kappa:Lambda ratio may indicate the presence of a monoclonal protein, which can be associated with conditions like multiple myeloma, MGUS, or other plasma cell disorders.
• Further workup for abnormal ratios typically includes serum protein electrophoresis, immunofixation, bone marrow biopsy, and imaging studies to determine the underlying cause and guide appropriate treatment.
• The Kappa:Lambda ratio is particularly useful when traditional serum protein electrophoresis might miss small monoclonal proteins, as noted in the 2017 study by the National Comprehensive Cancer Network (NCCN) 1.

From the Research

Kappa:Lambda Ratio

• The kappa:lambda ratio is used in the diagnosis of multiple myeloma, with different studies suggesting various cut-off values for this ratio.
• A study published in 2020 2 found that a kappa:lambda ratio of ≤1/7 or ≥9 yielded the highest diagnostic accuracy for multiple myeloma.
• Another study from 2012 3 discussed the role of serum protein electrophoresis in detecting multiple myeloma, but did not specifically address the kappa:lambda ratio.
• The use of interval-specific likelihood ratios can improve the clinical interpretation of serum free light chain (FLC) kappa:lambda ratio results for the diagnosis of malignant plasma cell disorders, as shown in a 2009 study 4.
• Serum protein electrophoresis is used to identify patients with multiple myeloma and other serum protein disorders, with a homogeneous spike-like peak in a focal region of the gamma-globulin zone indicating a monoclonal gammopathy 5.
• A 2015 study 6 found that an abnormal serum kappa/lambda light chain ratio is a common finding in patients with chronic kidney disease, but this does not necessarily indicate multiple myeloma.

Diagnostic Cut-Offs

• The cut-off values for the kappa:lambda ratio can vary depending on the study, with some suggesting ≤1/7 or ≥9 2 and others using ≤1/16 or ≥16.
• The choice of cut-off value can affect the diagnostic accuracy of the test, with some studies finding that certain cut-off values yield higher accuracy than others 2.
• The use of interval-specific likelihood ratios can help improve the clinical interpretation of serum FLC kappa:lambda ratio results 4.

Clinical Significance

• An abnormal kappa:lambda ratio can be a nonspecific finding in patients with proteinuria or chronic kidney disease 6.
• The kappa:lambda ratio should be interpreted in conjunction with other clinical and laboratory findings, such as serum protein electrophoresis and bone marrow biopsy results 2, 3, 5.