Laboratory Monitoring for Multiple Myeloma Recurrence
For monitoring possible recurrence of multiple myeloma, obtain serum protein electrophoresis (SPEP) with immunofixation (SIFE), serum free light chain (FLC) assay with kappa/lambda ratio, complete blood count (CBC), and serum chemistry panel including creatinine, albumin, calcium, LDH, and β2-microglobulin every 3-6 months, along with 24-hour urine protein electrophoresis (UPEP) with immunofixation (UIFE). 1, 2, 3
Core Laboratory Panel
Serum Tests (Every 3-6 Months)
Complete Blood Count (CBC): Monitor for anemia, leukopenia, and thrombocytopenia which indicate disease progression 1, 2, 3
Serum Chemistry Panel: Include creatinine (renal function), albumin (nutritional status and staging), calcium (hypercalcemia indicates active disease), LDH, and β2-microglobulin (prognostic markers) 1, 2, 3
Serum Quantitative Immunoglobulins: Track total IgG, IgA, and IgM levels to monitor disease burden 1, 2
Serum Protein Electrophoresis (SPEP) with Immunofixation (SIFE): This is the gold standard for detecting and quantifying the monoclonal protein (M-protein) 1, 2, 3
Serum Free Light Chain (FLC) Assay: Measure kappa and lambda free light chains with ratio calculation—this detects progression earlier than SPEP, often by 3 months 1, 2, 4
Urine Tests (Every 3-6 Months)
- 24-Hour Urine Collection: Obtain total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE)—random samples are insufficient 1, 2, 3
Why Free Light Chains Matter
The serum FLC assay is particularly valuable because it detects response and progression significantly earlier than traditional SPEP. Research demonstrates that involved free light chain (iFLC) detects progression with a median of 3 months earlier than SPEP, particularly in patients who progress more than 18 months after best response 4. This shorter half-life makes FLC an early independent predictor of disease status 4.
Additional Testing When Clinically Indicated
Bone Marrow Assessment
Bone marrow aspirate and biopsy: Perform when disease progression is suspected, to establish complete response, or when hyposecretory myeloma progression is suspected 1, 2, 3
Cytogenetic testing: Include FISH analysis for chromosome 17p13, t(4;14), and t(14;16) when evaluating progression 3
Imaging Studies
Annual bone survey or whole-body low-dose CT: Preferred over traditional skeletal survey for detecting new lytic lesions 2, 3
MRI and/or PET/CT: Use for suspected disease progression, evaluation of bone lesions, detection of extramedullary disease, or assessment of painful skeletal areas 1, 2, 3
PET imaging: Reliably predicts active myeloma through FDG uptake; smoldering myeloma is typically negative on PET scan 1, 2
Monitoring Frequency Based on Disease Status
Active Myeloma in Remission
Suspected Progressive or Relapsed Disease
- More frequent monitoring every 4 weeks initially 1
- Comprehensive reassessment including bone marrow examination, cytogenetic or FISH analyses, and imaging studies 2, 3
Critical Pitfalls to Avoid
Do not rely on random urine samples—always obtain 24-hour urine collections, as random samples miss significant light chain excretion 2, 3. The negative predictive value of combined negative SPEP and UPEP is 100%, meaning if both are negative, bone marrow biopsy for residual disease detection may be unnecessary 5.
Do not overlook rising free light chain levels even when SPEP appears stable—FLC elevation often precedes SPEP changes by months 2, 4. This is especially important in light chain-only or oligosecretory myeloma where SPEP may be falsely reassuring.
Do not use the same monitoring method throughout follow-up—patients with initially measurable disease by SPEP may become oligosecretory at relapse, requiring increased reliance on FLC assay 2.
Defining Disease Progression
Progressive disease is defined as a sustained 25% or greater increase in M-protein in serum or urine, greater than 25% increase in plasma cells in bone marrow, development of new lytic bone lesions, hypercalcemia, or increased size of bone lesions or plasmacytomas 1.