When should I consider Serum Protein Electrophoresis (SPEP) for multiple myeloma?

When to Consider SPEP for Multiple Myeloma

SPEP should be ordered when evaluating patients with unexplained anemia, renal insufficiency, hypercalcemia, bone lesions, or other clinical features suspicious for plasma cell disorders. 1

Indications for SPEP Testing

Clinical Scenarios Requiring SPEP

• Suspected plasma cell disorders:
  • Unexplained anemia
  • Renal insufficiency
  • Hypercalcemia
  • Bone lesions (especially lytic lesions)
  • Unexplained back pain
  • Recurrent infections
  • Hyperviscosity symptoms
  • Unexplained neuropathy

Specific Clinical Contexts

1. Initial evaluation of suspected multiple myeloma 2, 1

   • SPEP is a first-line test for detecting monoclonal proteins (M-proteins)
   • Should be part of the initial diagnostic workup when multiple myeloma is suspected

2. Monitoring known plasma cell disorders 2

   • For solitary plasmacytoma: Every 4 weeks initially, then every 3-6 months if paraprotein disappears
   • For smoldering myeloma: Every 3-6 months

3. Evaluation of unexplained lytic bone lesions 3

   • While SPEP has a sensitivity of 71% and specificity of 83% for plasma cell neoplasms
   • Negative predictive value is high (94%), making it useful to rule out myeloma

Limitations and Additional Testing

SPEP alone has limited sensitivity (71%) for detecting plasma cell disorders 3. Therefore, when ordering SPEP, consider complementary tests:

• Serum immunofixation electrophoresis (SIFE) - to characterize the protein type
• Serum free light chain (FLC) assay - to detect free kappa and lambda light chains
• 24-hour urine for protein electrophoresis (UPEP) and immunofixation (UIFE) - to detect monoclonal proteins in urine
• Quantitative immunoglobulins - to measure specific antibody types

Risk Stratification for MGUS

For patients with monoclonal gammopathy of undetermined significance (MGUS), SPEP testing frequency should be based on risk 2:

• Low-risk MGUS (M-protein <15 g/L, IgG type, normal FLC ratio):

  • Repeat SPEP in 6 months, then every 2-3 years if stable

• Intermediate/high-risk MGUS (M-protein >15 g/L, IgA or IgM type, or abnormal FLC ratio):

  • Bone marrow examination at baseline
  • Follow with SPEP and CBC in 6 months, then annually for life

Common Pitfalls to Avoid

1. Relying solely on SPEP - Due to limited sensitivity, complementary tests are essential 1

2. Overlooking nonsecretory disease - Approximately 3% of multiple myeloma patients have no detectable M-proteins on SPEP 1

3. Misinterpreting daratumumab treatment effects - Daratumumab may be detected on SPEP and immunofixation assays, causing false positive results 4

4. Failing to perform urine studies - Some patients excrete monoclonal proteins only in urine 5

5. Inconsistent testing methods - Using different methods for serial monitoring can lead to inaccurate assessment of disease progression 1

By following these guidelines for SPEP testing in suspected multiple myeloma, clinicians can ensure appropriate diagnosis, monitoring, and management of plasma cell disorders while avoiding common diagnostic pitfalls.