What are the symptoms and treatment options for multiple myeloma?

Multiple Myeloma: Symptoms and Treatment Options

Multiple myeloma is characterized by the CRAB criteria: hypercalcemia, renal insufficiency, anemia, and bone lesions, which represent the key symptoms requiring treatment initiation. 1

Symptoms

Primary Clinical Manifestations (CRAB Criteria)

• Hypercalcemia: Serum calcium >11.5 mg/dL (2.9 mmol/L), causing symptoms like fatigue, confusion, constipation, and thirst 1, 2
• Renal insufficiency: Serum creatinine >2.0 mg/dL or creatinine clearance <40 mL/min, leading to kidney dysfunction 1
• Anemia: Normochromic, normocytic with hemoglobin <10 g/dL or ≥2 g/dL below normal, resulting in weakness and fatigue 1, 3
• Bone lesions: Lytic lesions, severe osteopenia, or pathologic fractures, causing bone pain and risk of fractures 1, 4

Additional Common Symptoms

• Recurrent infections due to immune dysfunction 5
• Weakness and fatigue from anemia and disease burden 3
• Neurologic symptoms from vertebral compression, hyperviscosity, or hypercalcemia 4
• Weight loss and fever 5

Diagnostic Approach

Essential Diagnostic Tests

• Serum and urine protein electrophoresis: To detect and evaluate monoclonal (M-) component 1
• Immunoglobulin quantification: Measurement of IgG, IgA, and IgM levels 1
• Bone marrow examination: Aspiration and biopsy to assess plasma cell infiltration (≥10% clonal plasma cells required for diagnosis) 1, 6
• Skeletal imaging: Full skeleton X-ray survey to evaluate lytic bone lesions; MRI or CT for more detailed assessment when needed 1
• Complete blood count: To assess for anemia 1
• Serum calcium and creatinine: To evaluate for hypercalcemia and renal insufficiency 1

Treatment Options

Treatment Algorithm Based on Age and Transplant Eligibility

For Younger Patients (<65 years or fit patients)

• Induction therapy followed by high-dose therapy with autologous stem cell transplantation (ASCT) is the standard treatment 1
• Induction regimens:
  • Bortezomib-dexamethasone is superior to classical VAD regimen 1
  • Triple combinations such as VTD (bortezomib, thalidomide, dexamethasone) show higher response rates 1

For Elderly Patients (≥65 years or transplant-ineligible)

• Standard regimens:
  • Bortezomib, melphalan, prednisone (VMP) for 8-12 cycles 1, 6
  • Melphalan, prednisone, thalidomide (MPT) as an alternative option 1, 6
  • Daratumumab with lenalidomide and dexamethasone (DRd) has shown improved progression-free survival 7

Supportive Care

• Bone disease management:
  • Long-term bisphosphonates (zoledronic acid or pamidronate) to reduce skeletal-related events 1, 6, 4
  • Surgical intervention for vertebral compression or instability 4
• Hypercalcemia management:
  • Aggressive hydration with normal saline 6
  • Bisphosphonates for severe hypercalcemia 6
• Renal impairment:
  • Bortezomib-based regimens can be safely administered without dose adjustment 6
  • Avoid NSAIDs and maintain adequate hydration 6

Newer Treatment Approaches

• Immunomodulatory drugs: Thalidomide, lenalidomide, pomalidomide 5, 8
• Proteasome inhibitors: Bortezomib, carfilzomib 8
• Monoclonal antibodies: Daratumumab 7, 8
• Emerging therapies: Bispecific antibodies and CAR-T cell therapy 8, 9

Important Considerations

• Multiple myeloma is typically preceded by monoclonal gammopathy of undetermined significance (MGUS) and may progress through smoldering multiple myeloma (SMM) 1, 3
• Immediate treatment is not recommended for patients with indolent/smoldering myeloma 1
• Treatment should be initiated promptly in patients meeting CRAB criteria to reduce morbidity and mortality 6
• While multiple myeloma is generally considered incurable, newer therapies have significantly improved survival rates (5-7 years for newly diagnosed patients) 3, 9
• Careful monitoring for disease progression is essential in patients with precursor conditions (MGUS, SMM) 3