What is the diagnostic workup and treatment approach for a patient with suspected multiple myeloma?

Diagnostic Workup and Treatment Approach for Multiple Myeloma

The diagnostic workup for suspected multiple myeloma requires serum and urine protein electrophoresis, bone marrow evaluation, and skeletal imaging, while treatment is stratified based on transplant eligibility with combination therapies including proteasome inhibitors, immunomodulatory drugs, and corticosteroids. 1

Diagnostic Workup

Laboratory Tests

• Detection and evaluation of monoclonal (M-) protein through serum protein electrophoresis and urine protein electrophoresis (using 24-hour urine collection) 2
• Quantification of IgG, IgA, and IgM immunoglobulins 2
• Characterization of heavy and light chains of M-protein by immunofixation 2
• Complete blood count with differential to assess for anemia, leukopenia, and thrombocytopenia 3
• Serum chemistry including creatinine, calcium, albumin, LDH, and β2-microglobulin for staging and identifying end-organ damage 3, 1
• Serum free light chain (FLC) assay with kappa/lambda ratio, especially important for light chain myeloma 4

Bone Marrow Assessment

• Bone marrow aspiration and biopsy to detect quantitative and qualitative abnormalities of bone marrow plasma cells 2
• Cytogenetic studies including FISH analysis for prognostic stratification 4
• Flow cytometry to assess plasma cell abnormalities 4

Imaging Studies

• Full skeleton X-ray survey is the standard recommendation for evaluating lytic bone lesions 2
• MRI provides greater detail and is recommended if spinal cord compression is suspected 2
• CT and/or PET/CT may help distinguish between MGUS, smoldering myeloma, and overt myeloma 1

Staging and Risk Assessment

• The International Staging System (ISS) combining β2-microglobulin and serum albumin levels is used for prognostic stratification 1
• Cytogenetic abnormalities provide additional prognostic information 2
• Biological parameters including β2-microglobulin, C-reactive protein, LDH, and serum albumin have prognostic importance 2

Treatment Approach

Initial Treatment Decision

• Immediate treatment is not recommended for patients with indolent (smoldering) myeloma 1
• Treatment is indicated for symptomatic multiple myeloma with CRAB features (hypercalcemia, renal insufficiency, anemia, bone lesions) 1

Transplant-Eligible Patients (typically age ≤65 years, good clinical condition, no renal failure)

• High-dose therapy with autologous stem cell transplantation is the standard treatment 2
• Induction therapy with proteasome inhibitors (bortezomib), immunomodulatory drugs (lenalidomide), and dexamethasone 1, 5
• Peripheral blood progenitor cells should be used as the source of stem cells rather than bone marrow 2
• High-dose melphalan 200 mg/m² IV is the preferred preparative regimen prior to autologous transplantation 1

Transplant-Ineligible Patients (typically age >65-70 years or with significant comorbidities)

• Oral combination of melphalan (9 mg/m²/day for 4 days) and prednisone (30 mg/m²/day for 4 days) is a standard treatment option 2
• Cycles are repeated every 4-6 weeks until stable response is achieved 2
• Newer regimens including daratumumab in combination with lenalidomide and dexamethasone (DRd) have shown significant improvement in progression-free survival and overall survival compared to lenalidomide and dexamethasone alone 6

Supportive Care

• Long-term administration of bisphosphonates (oral or intravenous) reduces skeletal events and should be proposed for patients with stage III or relapsed disease 2
• Thromboprophylaxis is recommended, especially for patients receiving immunomodulatory drugs 7
• Prophylaxis against infections is important due to immunosuppression 7

Follow-Up Protocol

• Laboratory monitoring (CBC, serum chemistry, serum quantitative immunoglobulins, SPEP, SIFE, serum FLC) every 3-6 months 3
• Annual bone survey or as clinically indicated 3
• More frequent monitoring (every 4 weeks initially) for progressive or relapsed disease 3

Common Pitfalls and Caveats

• Failure to obtain 24-hour urine collections can lead to inadequate monitoring 3
• Missing extramedullary disease progression by not utilizing appropriate imaging 3
• Overlooking early signs of disease progression such as rising free light chain levels 3
• Multiagent chemotherapy has not proven superior and may be inferior in elderly patients 1
• When monitoring response with free light chain assays, it's crucial to use the same test for serial measurements 4