Multiple Myeloma: Comprehensive Workup and Management
Multiple myeloma requires a systematic diagnostic workup followed by risk-stratified treatment, with the goal of improving survival and quality of life through appropriate disease control and management of complications.
Diagnostic Workup
Initial Laboratory Assessment
- Complete blood count with differential and peripheral blood smear evaluation (looking for anemia, rouleaux formation, circulating plasma cells) 1
- Comprehensive chemistry panel including BUN, creatinine, electrolytes, calcium, albumin, and lactate dehydrogenase (LDH) 1
- Beta-2 microglobulin (important prognostic marker and measure of tumor burden) 1
Protein Studies
- Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) 1
- Quantitative immunoglobulin levels (IgG, IgA, IgM) 1
- Serum free light chain assay (essential for diagnosis, monitoring, and prognostication) 1
- 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE) 1
- Note: Random urine samples cannot replace 24-hour collections 1
Bone Marrow Assessment
- Bone marrow aspirate and biopsy (diagnosis confirmed when ≥10% clonal plasma cells are detected) 1, 2
- CD138 staining to accurately determine plasma cell percentage 1
- Immunophenotyping to establish clonality 1
- Cytogenetic studies including FISH for high-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, p53 mutation 1, 2
Imaging
- Skeletal survey including spine, pelvis, skull, humeri, and femurs 1
- Consider advanced imaging:
Diagnostic Criteria
Multiple Myeloma Defining Events
- CRAB features attributable to plasma cell disorder 2:
- Hypercalcemia (serum calcium >11 mg/dL)
- Renal insufficiency (creatinine >2 mg/dL or creatinine clearance <40 mL/min)
- Anemia (hemoglobin <10 g/dL or >2 g/dL below normal)
- Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures)
- Additional defining events 2:
- Bone marrow clonal plasmacytosis ≥60%
- Serum involved/uninvolved free light chain ratio ≥100 (provided involved FLC ≥100 mg/L)
1 focal lesion on MRI
Risk Stratification
Revised International Staging System
- Combines serum biomarkers (β2-microglobulin, albumin, LDH) with cytogenetic features 3
- High-risk features include 2:
- del(17p)
- t(4;14)
- t(14;16)
- t(14;20)
- gain 1q
- p53 mutation
- Double-hit myeloma: presence of any two high-risk factors 2
- Triple-hit myeloma: three or more high-risk factors 2
Management
Initial Treatment for Transplant-Eligible Patients
- Induction therapy with bortezomib, lenalidomide, dexamethasone (VRd) for 3-4 cycles 2
- For high-risk patients, consider daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) 2
- Followed by autologous stem cell transplantation (ASCT) 2, 3
- Maintenance therapy:
Initial Treatment for Transplant-Ineligible Patients
- VRd for approximately 8-12 cycles followed by maintenance 2
- Alternative: daratumumab, lenalidomide, dexamethasone (DRd) until progression 4, 2
- DRd has shown improved progression-free survival (PFS) and overall survival compared to Rd alone 4
Newer Treatment Options
- Carfilzomib-based regimens:
- Daratumumab-based combinations have shown significant improvement in outcomes 4
Supportive Care
- Thromboprophylaxis for patients on immunomodulatory drugs 5
- Bisphosphonate therapy for bone disease 7
- Prophylaxis against infections, particularly herpes zoster 5
- Adequate hydration, especially in patients at risk for tumor lysis syndrome or renal toxicity 5
Common Pitfalls and Considerations
- Relying solely on SPEP without immunofixation can miss approximately 30% of monoclonal gammopathies 8
- Random urine samples cannot replace 24-hour urine collections for accurate protein assessment 1
- Serum albumin measurement method matters - bromcresol method correlates better with nephelometric quantitation when monoclonal protein levels are high 1
- Patients require monitoring for treatment-related complications including: