What is the evaluation and management approach for a patient with elevated light chains?

Evaluation and Management of Elevated Light Chains

The diagnostic workup for a patient with elevated light chains should include serum creatinine measurement, electrolytes assessment, estimated glomerular filtration rate (eGFR), 24-hour urine collection with electrophoresis, serum protein electrophoresis, and serum free light chain measurement to determine the underlying cause and guide appropriate management. 1

Diagnostic Evaluation

Initial Laboratory Tests

• Serum creatinine, electrolytes, and eGFR to assess renal function 1
• Serum protein electrophoresis (SPEP) - quantitative, easy to perform, and inexpensive 1
• Serum immunofixation electrophoresis (SIFE) - more sensitive than SPEP for identifying and typing monoclonal immunoglobulins 1
• Serum free light chain assay (SFLCA) - measures κ and λ free light chains independently and determines the κ:λ ratio 1
• 24-hour urine collection with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) 1

Interpretation of Free Light Chain Results

• Normal κ:λ free light chain ratio is 0.26-1.65 1
• In severe renal impairment (CKD stage 5), the normal ratio can rise to 0.34-3.10 1
• A high ratio indicates a κ clone, while a low ratio indicates a λ clone 1
• Be aware that the same assay (FreeLite or N Latex) must be used throughout monitoring as results are not mathematically convertible 1
• Lambda chain lesions may be under-detected in approximately 25% of cases 2

Additional Diagnostic Considerations

• Renal biopsy should be considered if the cause of renal insufficiency cannot be clearly attributed to myeloma 1
• Bone marrow biopsy or aspirate may be needed to assess plasma cell clones 1
• Imaging techniques may be required to evaluate organ involvement, particularly for suspected amyloidosis 1

Management Approach

For Light Chain Cast Nephropathy

• Initiate bortezomib-containing regimens as soon as possible to decrease production of nephrotoxic clonal immunoglobulin 1
• Bortezomib/dexamethasone can be administered to patients with severe renal impairment without dose adjustment 1
• Consider adding a third drug that doesn't require dose adjustment (cyclophosphamide, thalidomide, anthracycline, or daratumumab) 1
• Provide adequate hydration and urine alkalinization 1
• Treat hypercalcemia if present 1

For AL Amyloidosis

• Evaluate for cardiac involvement using cardiac biomarkers (troponin T, NT-proBNP) 1
• Consider autologous stem cell transplantation (ASCT) for eligible patients 1
• For patients ineligible for ASCT, consider bortezomib-based regimens 1
• Monitor organ function and response to therapy 1

For Other Monoclonal Gammopathies of Renal Significance (MGRS)

• Treatment should target the underlying plasma cell or B-cell clone 1
• Therapy selection depends on the specific type of renal lesion and the underlying clonal disorder 1

Monitoring Response

• Use the same serum free light chain assay throughout treatment 1
• Monitor renal function regularly 1
• The heavy/light chain (HLC) assay may provide additional information for monitoring disease and detecting residual disease 3
• Highly abnormal HLC ratios at presentation are associated with shorter overall survival 3

Important Caveats

• Renal impairment alters free light chain concentration due to impaired clearance 1
• Avoid nephrotoxic medications such as NSAIDs in patients with elevated light chains 1
• Consider dose adjustments for medications based on renal function 1
• Lambda light chains may be underproduced relative to kappa chains in some patients, potentially affecting detection 2
• Elevated free light chains can be either monoclonal or polyclonal, with different prognostic implications 4