What is the basic workout plan for patients with multiple myeloma?

Basic Workup for Multiple Myeloma

The basic workup for multiple myeloma requires demonstration of clonal bone marrow plasma cells ≥10% or biopsy-proven plasmacytoma, plus evidence of end-organ damage (CRAB criteria: hypercalcemia, renal insufficiency, anemia, bone lesions) or specific biomarkers including ≥60% clonal plasma cells, involved/uninvolved free light chain ratio ≥100, or MRI with more than one focal lesion. 1

Initial Diagnostic Assessment

Laboratory Studies:

• Serum and urine protein electrophoresis to identify and quantify monoclonal protein (M-protein) 1
• Serum free light chain assay with calculation of involved/uninvolved ratio 1
• Complete blood count to assess for anemia (hemoglobin <10 g/dL or >2 g/dL below normal) 1
• Comprehensive metabolic panel including:
  • Serum calcium (corrected calcium >11 mg/dL indicates hypercalcemia) 1
  • Serum creatinine (>2 mg/dL indicates renal insufficiency) 1
  • Serum albumin for staging purposes 1, 2
• Beta-2 microglobulin - this is one of the most important prognostic parameters and reflects tumor burden 2
• Lactate dehydrogenase (LDH) for risk stratification 1

Bone Marrow Evaluation:

• Bone marrow aspiration and biopsy to quantify plasma cell percentage and assess morphology 1
• Cytogenetics and FISH studies to identify high-risk abnormalities including t(4;14), t(14;16), t(14;20), del(17p), gain 1q, or p53 mutation 1

Imaging Studies:

• Whole-body low-dose CT or PET-CT as preferred imaging modality to detect lytic bone lesions 1
• MRI of spine and pelvis if CT is negative but clinical suspicion remains high, or to evaluate for focal lesions (>1 focal lesion is diagnostic even without CRAB features) 1
• Skeletal survey is an alternative if advanced imaging unavailable, though less sensitive 1

Staging and Risk Stratification

International Staging System (ISS):

• Stage I: Beta-2 microglobulin <3.5 mg/L and albumin ≥3.5 g/dL 1, 2
• Stage II: Neither Stage I nor III 1
• Stage III: Beta-2 microglobulin ≥5.5 mg/L 1, 2

Revised ISS (R-ISS) incorporates high-risk cytogenetics and LDH in addition to ISS parameters for more refined prognostication 1

Critical Assessment for Treatment Planning

Transplant Eligibility Determination:

• Assess age, performance status (ECOG or Karnofsky), and comorbidities to determine if patient is transplant-eligible 1
• Evaluate cardiac, pulmonary, renal, and hepatic function 1

Bone Disease Assessment:

• Document presence and location of lytic lesions, pathological fractures, or spinal cord compression 1, 3
• If spinal cord compression present: Immediate high-dose dexamethasone and urgent evaluation for surgical decompression if due to bone fragments 3
• If neurologic impairment: Local radiotherapy indicated 3

Important Caveats

Beta-2 microglobulin interpretation: Renal dysfunction can artificially elevate levels independent of tumor burden since it is cleared by the kidneys - interpret cautiously in patients with renal insufficiency 2

Minimal residual disease (MRD) assessment: Should be performed in patients achieving complete response, as MRD negativity correlates with prolonged progression-free and overall survival 1

Monitoring frequency: Check M-protein (serum/urine electrophoresis) after 1-2 cycles initially to ensure no progression, then every other cycle during active treatment 1