What is the workup for multiple myeloma after a positive Serum Protein Electrophoresis (SPEP)?

From the Guidelines

The workup for multiple myeloma after a positive Serum Protein Electrophoresis (SPEP) should include a comprehensive evaluation to confirm the diagnosis and assess disease burden, as outlined in the most recent guidelines from 2017 1. To initiate the workup, begin with serum immunofixation to identify the specific monoclonal protein, quantitative immunoglobulins (IgG, IgA, IgM), and serum free light chain assay to measure kappa and lambda free light chains and their ratio, as these tests provide crucial information for diagnosis and prognosis 1. The following steps should be undertaken:

• Complete a 24-hour urine collection for protein electrophoresis and immunofixation to evaluate the presence and quantity of monoclonal protein in the urine 1.
• Order a complete blood count, comprehensive metabolic panel (including calcium, creatinine, albumin), beta-2 microglobulin, and LDH for staging and prognosis, as these tests help assess the extent of disease and potential end-organ damage 1.
• Imaging studies should include a skeletal survey or low-dose whole-body CT scan to detect bone lesions, with MRI or PET-CT considered for more detailed evaluation, especially in cases where bone lesions are suspected or identified 1.
• A bone marrow biopsy with aspirate is essential to quantify plasma cell percentage, assess morphology, and perform cytogenetics and FISH testing for prognostic markers like t(4;14), t(14;16), and del(17p), which are critical for determining the risk stratification and guiding treatment decisions 1. Additional tests may include viscosity if IgM paraprotein is high, and assessment for end-organ damage (CRAB features: hypercalcemia, renal insufficiency, anemia, bone lesions), as these factors influence the diagnosis of symptomatic multiple myeloma and the need for immediate treatment 1. This comprehensive workup allows for accurate diagnosis, staging according to the Revised International Staging System (R-ISS), and helps determine if the patient has smoldering myeloma or symptomatic disease requiring immediate treatment, thereby prioritizing morbidity, mortality, and quality of life outcomes 1.

From the Research

Workup for Multiple Myeloma

After a positive Serum Protein Electrophoresis (SPEP), the workup for multiple myeloma involves several steps:

• Bone marrow biopsy to assess the percentage of clonal bone marrow plasma cells 2
• Imaging studies, such as magnetic resonance imaging (MRI), to detect lytic bone lesions or focal lesions 2
• Serum and urine protein electrophoresis (SPEP and UPEP) to identify and quantify monoclonal protein 3, 4, 5
• Serum free light chain (FLC) assay to assess the involved/uninvolved FLC ratio 2, 3, 4
• Immunofixation electrophoresis (IFE) to confirm and type the monoclonal protein 3, 5
• Fluorescence in situ hybridization (FISH) and other genetic tests to detect high-risk cytogenetic abnormalities, such as del(17p), t(4;14), and p53 mutation 2, 5

Diagnostic Criteria

The diagnosis of multiple myeloma requires one or more of the following:

• Clonal bone marrow plasma cells ≥10% 2
• Biopsy-proven plasmacytoma 2
• Any one of the following multiple myeloma defining events (MDE):
  • Hypercalcemia, renal failure, anemia, or lytic bone lesions (CRAB) attributable to the plasma cell disorder 2
  • Bone marrow clonal plasmacytosis ≥60% 2
  • Serum involved/uninvolved FLC ratio ≥100 (provided involved FLC is ≥100 mg/L and urine monoclonal protein is ≥200 mg/24 h) 2

  • 1 focal lesion on MRI 2

Monitoring and Prognosis

Monitoring of multiple myeloma involves regular assessment of:

• Serum and urine protein electrophoresis (SPEP and UPEP) 3, 4, 5
• Serum free light chain (FLC) assay 2, 3, 4
• Minimal residual disease (MRD) status 6 The prognosis of multiple myeloma is influenced by various factors, including the presence of high-risk cytogenetic abnormalities, the depth of response to treatment, and the MRD status 2, 6