What is the interpretation of a change in serum protein electrophoresis (SPEP) results in a male patient with multiple myeloma, from a total protein of 8.22 g and albumin to globulin (A/G) ratio of 0.66 to a total protein of 6.63 g and A/G ratio of 1.71?

Interpretation of SPEP Changes in Multiple Myeloma

The dramatic improvement in your SPEP results—with total protein decreasing from 8.22 g to 6.63 g and A/G ratio normalizing from 0.66 to 1.71—strongly suggests an excellent response to treatment, indicating significant reduction in monoclonal protein burden. 1, 2

Understanding the Changes

Total Protein Reduction

• The decrease in total protein from 8.22 g to 6.63 g reflects reduction in the monoclonal protein (M-protein) produced by malignant plasma cells 2
• In multiple myeloma, elevated total protein is primarily driven by excessive production of abnormal immunoglobulins, and its decline indicates disease control 3

Albumin/Globulin (A/G) Ratio Normalization

• The A/G ratio improvement from 0.66 (abnormally low) to 1.71 (normal range) is particularly significant 2, 3
• A low A/G ratio in myeloma indicates disproportionately elevated globulins (where M-protein resides) relative to albumin 3
• Normalization to 1.71 suggests the globulin fraction has decreased substantially, indicating reduction or elimination of the M-protein spike 2, 3

Clinical Significance for Disease Monitoring

Response Assessment Framework

• According to ASCO/CCO guidelines, all measurable parameters including serum protein electrophoresis must be followed to assess treatment response 1
• The NCCN recommends SPEP as a fundamental tool for quantifying M-protein levels to track disease progression and monitor treatment response 1, 2
• Changes in M-protein concentration over time using SPEP are the primary method for determining treatment efficacy 1, 2

What These Results Likely Indicate

• This pattern is consistent with at least a partial response (PR) or possibly very good partial response (VGPR) to therapy 1
• The normalization of the A/G ratio suggests substantial reduction in the monoclonal component 2, 3
• However, SPEP alone cannot definitively categorize the depth of response according to IMWG criteria 1

Essential Next Steps for Complete Assessment

Required Confirmatory Testing

To properly classify the response depth and confirm these favorable findings, the following tests are mandatory: 1, 2

• Serum immunofixation electrophoresis (SIFE) to determine if the M-protein is still detectable and to confirm its type 1, 4
• Quantitative immunoglobulin levels (IgG, IgA, IgM) to assess the specific monoclonal immunoglobulin and check for immune paresis 1, 4
• Serum free light chain (FLC) assay with kappa/lambda ratio for sensitive monitoring, especially important as disease can evolve to light chain escape 1, 2
• 24-hour urine protein electrophoresis and immunofixation if there was measurable urinary M-protein at baseline 1

Response Confirmation Requirements

• All responses must be confirmed per IMWG criteria (excluding marrow and imaging), which can be done with repeat testing from a separate blood draw 1
• This confirmation ensures laboratory variations are accounted for 1

Critical Monitoring Considerations

Ongoing Surveillance

• Response assessment should be performed after each cycle initially, then every other cycle once a response trend is observed, and less frequently once in plateau phase 1
• For patients with active myeloma, quantitative immunoglobulins plus M-protein quantitation should be done at least every 3 months 4

Important Caveats

• Approximately 15-20% of myeloma cases can develop "light chain escape" where disease evolves to produce only light chains, which may not be adequately captured by standard SPEP 1, 2
• Serum free light chain levels should be followed in addition to SPEP to detect this phenomenon 1
• Some patients (1-3%) have non-secretory myeloma with no detectable M-protein, requiring alternative monitoring methods 1, 2

Albumin Measurement Accuracy

• If using albumin levels for prognostic staging (ISS/R-ISS), be aware that bromcresol green (BCG) method is more reliable than protein electrophoresis-derived albumin in the presence of M-spikes 5
• Protein electrophoresis can overestimate albumin when significant M-protein is present 5

Bottom Line

Your results demonstrate favorable disease response with substantial reduction in tumor burden, but complete response classification requires the additional confirmatory tests outlined above, particularly serum immunofixation and free light chain analysis. 1, 4, 2