Initial Treatment for Multiple Myeloma
The standard initial treatment for multiple myeloma is bortezomib, lenalidomide, and dexamethasone (VRd) regardless of transplant eligibility, followed by autologous stem cell transplantation in eligible patients and lenalidomide maintenance until progression. 1, 2
Induction Therapy
All patients with newly diagnosed multiple myeloma should receive VRd as the preferred triplet regimen. 3, 1, 2 This applies to both transplant-eligible and transplant-ineligible patients, as VRd delivers response rates of approximately 90% (VGPR or better) and has become the backbone for initial therapy. 4
VRd Dosing Schedule
- Bortezomib: 1.3 mg/m² subcutaneously on days 1,8,15,22 every 3 weeks (subcutaneous route significantly reduces peripheral neuropathy risk compared to IV) 3, 5
- Lenalidomide: 25 mg orally days 1-14 every 3 weeks 3
- Dexamethasone: 20 mg on day of and day after bortezomib (or 40 mg on days 1,8,15,22) 3
Duration of Induction
- Transplant-eligible patients: 3-4 cycles of VRd followed by stem cell collection and autologous transplantation 6, 7
- Transplant-ineligible patients: 8-12 cycles of VRd followed by maintenance therapy 6, 7
Risk-Stratified Modifications
High-risk cytogenetics [del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation] warrant consideration of daratumumab-VRd (Dara-VRd) instead of standard VRd. 6, 7 This four-drug combination provides enhanced disease control in patients with adverse genetic features.
Standard-risk patients should proceed with VRd as outlined above. 1, 2
Autologous Stem Cell Transplantation
Transplant-eligible patients should proceed to high-dose melphalan (200 mg/m²) with autologous stem cell transplantation after induction. 1 Peripheral blood progenitor cells are preferred over bone marrow as the stem cell source. 1
Selected standard-risk patients may delay transplantation until first relapse after collecting and storing stem cells, continuing with additional cycles of induction therapy instead. 6, 7
Maintenance Therapy
Lenalidomide maintenance should be continued until disease progression for standard-risk patients. 1, 2 This provides median progression-free survival of 41 months post-transplant. 5
High-risk patients require bortezomib-based maintenance therapy rather than lenalidomide alone. 1, 2, 6 The combination of bortezomib plus lenalidomide is preferred for patients with adverse cytogenetics. 6, 7
Essential Supportive Care Measures
Thromboprophylaxis is mandatory for all patients receiving lenalidomide-based therapy. 1, 5, 2 Full-dose aspirin or therapeutic anticoagulation must be initiated to prevent thromboembolic complications. 2
Herpes zoster prophylaxis should be administered to all patients treated with proteasome inhibitors (bortezomib). 5, 2
Bisphosphonates must be given to reduce skeletal-related events. 1, 5
Response Monitoring
Response assessment should occur with each treatment cycle using serum and urine protein electrophoresis plus serum free light chains. 5, 2 Once best response is achieved or during maintenance, assessment frequency may decrease to every 3 months minimum. 2
Complete response requires <5% plasma cells in bone marrow and negative immunofixation. 1, 5
Whole-body low-dose CT is preferred over conventional skeletal survey for bone assessment. 1, 2
Critical Pitfalls to Avoid
Do not use intravenous bortezomib when subcutaneous administration is available - the subcutaneous route significantly reduces peripheral neuropathy rates while maintaining equivalent efficacy. 3, 5, 2
Do not omit thromboprophylaxis in patients on immunomodulatory drugs - lenalidomide carries substantial thrombotic risk that requires prophylactic anticoagulation. 1, 5, 2
Do not use fixed-duration therapy when continuous therapy is appropriate - for transplant-ineligible patients, continuous lenalidomide maintenance until progression provides superior outcomes compared to stopping after a fixed number of cycles. 2
Alternative Regimens (When VRd Cannot Be Used)
If VRd is contraindicated, alternative triplet regimens include:
- Bortezomib/cyclophosphamide/dexamethasone (VCD) 3
- Bortezomib/thalidomide/dexamethasone (VTD) 3
- Daratumumab/lenalidomide/dexamethasone (DRd) for transplant-ineligible patients 7
However, these are second-line choices when VRd cannot be administered. 1, 2