Multiple Myeloma: Typical Presentation and Treatment
Multiple myeloma typically presents with bone pain, anemia, renal impairment, and hypercalcemia, requiring treatment based on transplant eligibility with novel agent combinations including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. 1, 2
Clinical Presentation
Common Presenting Features (CRAB Criteria)
- Hypercalcemia: Serum calcium >11.0 mg/dL 1
- Renal insufficiency: Serum creatinine >2.0 mg/dL 1
- Anemia: Hemoglobin <10 g/dL or 2 g/dL below lower limit of normal 1
- Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures 1, 2
Additional Presenting Symptoms
- Fatigue and malaise due to anemia 3, 4
- Recurrent infections due to immune dysfunction 5
- Hyperviscosity symptoms (rare): visual disturbances, neurological symptoms 5
- Extramedullary disease in advanced cases 1
Diagnostic Evaluation
Essential Laboratory Tests
- Serum protein electrophoresis (SPEP) and immunofixation to detect monoclonal protein 1
- Urine protein electrophoresis (UPEP) on 24-hour collection 1
- Quantification of IgG, IgA, and IgM immunoglobulins 1
- Serum free light chain assay with kappa/lambda ratio 6
- Complete blood count, serum creatinine, calcium, LDH, and β2-microglobulin 1, 6
Bone Marrow Assessment
- Bone marrow aspiration and biopsy to quantify plasma cell infiltration 1
- Cytogenetic analysis by FISH to detect high-risk features (t(4;14), del(17p), t(14;16)) 1, 2
Imaging Studies
- Full skeletal survey (X-rays) to detect lytic bone lesions 1
- MRI provides greater detail and is recommended if spinal cord compression is suspected 1
- PET/CT can help assess extent of disease and detect extramedullary involvement 1, 6
Treatment Approach
Initial Stratification
- Determine transplant eligibility based on age, performance status, and comorbidities 1
- Assess risk status using International Staging System (ISS) or Revised ISS 1, 2
- Identify high-risk cytogenetic features that may impact treatment choices 1
Treatment of Smoldering (Asymptomatic) Myeloma
- Observation without immediate treatment is recommended 1
- Monitor at 3-6 month intervals with laboratory tests 1, 6
- Consider clinical trials for high-risk smoldering myeloma 1
Treatment of Symptomatic Myeloma in Transplant-Eligible Patients (<65 years or fit)
- Induction therapy with three-drug regimens including bortezomib and dexamethasone plus another agent 1
- Preferred regimens include:
- High-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation 1
- Maintenance therapy with lenalidomide to prolong remission 2
Treatment of Symptomatic Myeloma in Transplant-Ineligible Patients
- Oral combination regimens are standard of care 1:
- Bendamustine plus prednisone for patients with clinical neuropathy 1
Treatment of Relapsed Disease
- Triplet therapy is recommended over doublet therapy at first relapse 1
- Triplet regimens contain two novel agents (proteasome inhibitor, immunomodulatory drug, or monoclonal antibody) plus steroids 1
- Treatment selection should consider prior therapies, response duration, and toxicities 1
Supportive Care
Bone Disease Management
- Long-term bisphosphonates to reduce skeletal events 1
- Pain management with appropriate analgesics (avoid nephrotoxic NSAIDs) 5
- Radiotherapy for painful lesions 8
- Vertebroplasty or kyphoplasty for vertebral compression fractures 5
Management of Complications
- Hypercalcemia: IV fluids, steroids, furosemide, bisphosphonates 5
- Renal dysfunction: Maintain hydration, avoid nephrotoxic agents 5
- Infections: Prompt use of broad-spectrum antibiotics for febrile illness 5
- Anemia: Erythropoiesis-stimulating agents if symptomatic 5
Follow-Up and Monitoring
Laboratory Monitoring
- CBC, serum chemistry, quantitative immunoglobulins, SPEP/SIFE, and serum free light chain assay every 3-6 months 6
- 24-hour urine collection for total protein and UPEP/UIFE 6
Imaging Follow-Up
- Annual bone survey or as clinically indicated 6
- MRI, CT, or PET/CT as needed for suspected progression 6