What is the initial treatment for a patient with multiple myeloma and a positive bone aspirate?

Initial Treatment for Multiple Myeloma with Positive Bone Aspirate

The initial treatment for a patient with multiple myeloma and a positive bone aspirate should be a triplet regimen consisting of bortezomib, lenalidomide, and dexamethasone (VRd) for transplant-eligible patients, or bortezomib, melphalan, and prednisone (VMP) for transplant-ineligible patients. 1

Treatment Algorithm Based on Transplant Eligibility

For Transplant-Eligible Patients (typically <65 years or fit patients)

1. Induction Therapy:

   • VRd (bortezomib, lenalidomide, dexamethasone) for 3-4 cycles 1, 2
   • Alternative options include:
     • VTD (bortezomib, thalidomide, dexamethasone) 2
     • VCD (bortezomib, cyclophosphamide, dexamethasone) 2

2. Stem Cell Collection and Transplantation:

   • High-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation (ASCT) 1
   • Consider 2-3 additional cycles of consolidation therapy post-transplant 2

3. Maintenance Therapy:

   • Lenalidomide until progression for standard-risk patients 1
   • Bortezomib plus lenalidomide for high-risk patients 1

For Transplant-Ineligible Patients (typically >65 years)

1. Initial Treatment:
   • VMP (bortezomib, melphalan, prednisone) for 9 cycles 2, 1
   • Alternative options:
     • MPT (melphalan, prednisone, thalidomide) 2
     • Rd (lenalidomide, low-dose dexamethasone) continuously until progression 1

Dosing Recommendations

VRd Regimen:

• Bortezomib: 1.3 mg/m² subcutaneously days 1,8,15 1
• Lenalidomide: 25 mg orally days 1-14 1
• Dexamethasone: 20 mg on day of and day after bortezomib (or 40 mg days 1,8,15,22) 1

VMP Regimen:

• Bortezomib: 1.3 mg/m² subcutaneously days 1,4,8,11,22,25,29,32 (cycles 1-4), then days 1,8,22,29 (cycles 5-9) 3
• Melphalan: 9 mg/m² orally days 1-4 3
• Prednisone: 60 mg/m² orally days 1-4 3

Important Considerations

• Subcutaneous bortezomib is preferred over intravenous administration to reduce the risk of peripheral neuropathy 1
• Dose adjustments may be necessary for elderly or frail patients, such as reduced dexamethasone (8-20 mg weekly) for patients >75 years 1
• Renal function should be monitored closely, as bortezomib-based regimens generally don't require dose adjustment for renal impairment 1
• Thromboprophylaxis is recommended for patients on immunomodulatory drugs (lenalidomide, thalidomide) 1
• Herpes zoster prophylaxis should be provided for patients on proteasome inhibitors (bortezomib) 1

Response Evaluation

• Evaluate response after each cycle during induction 1
• Response criteria include:
  • Complete response (CR): Negative serum/urine immunofixation, <5% plasma cells in bone marrow 2
  • Very good partial response (VGPR): ≥90% reduction in serum M-protein 2
  • Partial response (PR): ≥50% reduction in serum M-protein, ≥90% reduction in 24-h urine M-protein 2

Supportive Care

• Bisphosphonates to reduce skeletal-related events 1
• Pain management for bone lesions, including analgesics and localized radiation therapy if needed 2
• Treatment of hypercalcemia with IV fluids and bisphosphonates if present 2
• Anemia management with erythropoiesis-stimulating agents when appropriate 4

The evidence strongly supports the use of triplet regimens containing a proteasome inhibitor (bortezomib) as the backbone of initial therapy for multiple myeloma, with treatment selection guided by transplant eligibility and patient-specific factors such as age, comorbidities, and cytogenetic risk status.