From the Guidelines
The kappa/lambda ratio is a crucial diagnostic and monitoring tool in multiple myeloma, with a normal serum free light chain ratio ranging from 0.26-1.65, as defined by the International Myeloma Working Group (IMWG) criteria 1.
Importance of Kappa/Lambda Ratio
The kappa/lambda ratio helps distinguish between monoclonal gammopathies and reactive processes, aids in diagnosis when traditional electrophoresis is negative, and serves as a sensitive marker for monitoring disease response to treatment.
- Changes in the ratio often precede clinical manifestations of disease progression or response.
- For patients with renal impairment, interpretation requires caution as kidney dysfunction can alter light chain clearance.
- Serial measurements of the kappa/lambda ratio are more valuable than single readings, allowing clinicians to track treatment effectiveness and detect early relapse.
Clinical Application
The ratio should be interpreted alongside other clinical parameters including bone marrow findings, imaging studies, and other laboratory markers for comprehensive disease assessment.
- According to the IMWG criteria, a normal FLC ratio is required for complete response (CR) definition, in addition to other criteria such as negative immunofixation on serum and urine, and disappearance of any soft tissue plasmacytomas 1.
- The current treatment algorithms for multiple myeloma incorporate the kappa/lambda ratio as a diagnostic and monitoring tool, alongside other parameters such as bone marrow clonal plasma cells, serum involved to uninvolved free light chain (FLC) ratio, and magnetic resonance imaging (MRI) findings 1.
Monitoring and Treatment
In clinical practice, the kappa/lambda ratio should be used in conjunction with other diagnostic and monitoring tools to guide treatment decisions and assess disease response in multiple myeloma patients 1.
- The ratio can help identify patients with high-risk disease, such as those with a significantly skewed kappa/lambda ratio (>100 or <0.01), who may require more aggressive treatment.
- Serial measurements of the kappa/lambda ratio can help detect early relapse and guide treatment adjustments to improve patient outcomes.
From the Research
Kappa Lambda Ratio in Multiple Myeloma
- The kappa/lambda ratio is used to diagnose multiple myeloma, with different studies suggesting various cut-off values for diagnosis 2, 3.
- A study published in 2020 found that a kappa/lambda ratio of ≤1/7 or ≥9 yielded the highest diagnostic accuracy for multiple myeloma, with an area under the receiver operating characteristic curve of 1.0000 2.
- Another study published in 2012 found that a kappa/lambda ratio between 0.59 and 4.0 could distinguish plasma cell myeloma cells from normal plasma cells, with a sensitivity of 94.7% and a specificity of 94.7% 3.
- The diagnosis of multiple myeloma typically involves a combination of clinical, laboratory, and imaging tests, including measurement of serum free light chain levels, serum protein electrophoresis, and full-body skeletal imaging 4, 5.
- The Revised International Staging System is used to assess the prognosis of multiple myeloma patients, based on factors such as serum biomarkers and malignant plasma cell genomic features 4, 5.
Diagnostic Criteria
- The diagnosis of multiple myeloma requires the presence of ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma, plus evidence of one or more multiple myeloma defining events (MDE) 5.
- MDE include CRAB features (hypercalcemia, renal failure, anemia, or lytic bone lesions), bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain ratio ≥100, or >1 focal lesion on magnetic resonance imaging (MRI) 5.
Treatment Options
- Standard first-line therapy for multiple myeloma typically consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide 4, 5.
- High-risk patients may require alternative therapies, such as daratumumab, bortezomib, lenalidomide, and dexamethasone 5.