From the Guidelines
Elevated kappa free light chains and an elevated free light chain ratio with a normal immunofixation is highly suggestive of monoclonal gammopathy of undetermined significance (MGUS) or early multiple myeloma, and requires further evaluation and regular monitoring to watch for progression to multiple myeloma or related disorders. This pattern indicates that there is an excess production of kappa light chains by plasma cells, but not enough to create complete immunoglobulins that would be detected on immunofixation 1. The abnormal free light chain ratio is significant because it reflects clonal plasma cell proliferation, even when traditional tests like immunofixation are normal.
Key Considerations
- The European Myeloma Network recommends follow-up according to risk of progression and life expectancy, with low-risk MGUS and light-chain MGUS requiring follow-up at 6 months, and annually thereafter if life expectancy is ≥5 years 1.
- Further evaluation should include a complete blood count, comprehensive metabolic panel, serum calcium, and a bone marrow biopsy to determine the percentage of plasma cells.
- Imaging studies such as a skeletal survey, low-dose CT, or MRI may be needed to check for bone lesions.
- Regular monitoring should also include careful history, physical examination, and laboratory studies, including quantification of M-protein, complete blood count, creatinine, and calcium 1.
Monitoring and Follow-up
- Patients with an abnormal free light-chain ratio with elevation of the involved light-chain should also have NT-pro-BNP and urinary albumin monitored during follow-up to detect organ damage caused by light chains 1.
- Patients should be instructed to contact their physician if there is any change in their clinical condition, and further investigations are indicated if new symptoms or signs develop that are suggestive of underlying MM, WM, or AL amyloidosis, or if a patient has abnormal laboratory results 1.
From the Research
Elevated Kappa Free Light Chain and Elevated Light Chain Ratio but Normal Immunofixation
- Elevated kappa free light chain and elevated light chain ratio can be indicative of multiple myeloma, a type of blood cancer characterized by the proliferation of malignant plasma cells in the bone marrow 2, 3.
- However, a normal immunofixation result can make the diagnosis more challenging, as immunofixation is a test used to detect and identify abnormal proteins in the blood or urine 4.
- Studies have shown that an abnormal serum free light chain ratio can be associated with known prognostic factors in lymphoma, such as the international prognostic index (IPI) and B symptoms 5.
- In the context of multiple myeloma, the serum free light chain ratio, total kappa/lambda ratio, and immunofixation results may not be prognostic factors after stem cell transplantation for newly diagnosed patients 6.
- The kappa/lambda ratio can be used to diagnose multiple myeloma, with cut-offs of ≤1/7 or ≥9 yielding the highest diagnostic accuracy 4.
- Elevated levels of beta-2 microglobulin (β2-MG) and serum creatinine, as well as decreased hemoglobin levels, can be associated with an elevated serum free light chain kappa/lambda ratio in patients with multiple myeloma 3.