VRD Guidelines for Multiple Myeloma
VRD (bortezomib, lenalidomide, and dexamethasone) is a category 1, preferred regimen for multiple myeloma treatment, particularly as induction therapy for transplant-eligible patients, offering superior progression-free and overall survival compared to doublet regimens. 1
Standard VRD Dosing Regimen
The standard VRD regimen consists of:
- Bortezomib: 1.3 mg/m² subcutaneously on days 1,8,15 1
- Lenalidomide: 25 mg orally on days 1-14 1
- Dexamethasone: 20 mg on day of and day after bortezomib (or 40 mg on days 1,8,15,22) 1
- Cycle repeats every 3 weeks 1
Clinical Evidence Supporting VRD
Efficacy in Newly Diagnosed Multiple Myeloma
The SWOG S0777 trial demonstrated significantly improved outcomes with VRD compared to Rd (lenalidomide-dexamethasone) alone: 1, 2
- Median progression-free survival: 43 months vs 30 months (HR 0.712)
- Median overall survival: 75 months vs 64 months (HR 0.709)
- With longer follow-up (median 84 months), PFS benefit maintained (41 vs 29 months) 1
Response rates with VRD induction: 3
- Overall response rate: 97.1%
- Very good partial response or better: 89.9% after transplantation
- Stringent complete response: 33.3% after transplantation
VRD vs Other Regimens
- The ENDURANCE trial compared VRD to KRd (carfilzomib, lenalidomide, dexamethasone) in standard-risk patients: 1, 4
- Similar PFS: 34.4 months (VRD) vs 34.6 months (KRd)
- VGPR or better: 65% (VRD) vs 74% (KRd)
- VRD had more peripheral neuropathy but fewer cardiac, pulmonary, and renal toxicities 1
Modified VRD Regimens
VRD-lite for Elderly/Frail Patients
For patients who may not tolerate standard VRD, a modified "VRD-lite" regimen can be considered: 1, 5
Bortezomib: 1.3 mg/m² subcutaneously on days 1,8,15, and 22 1
Lenalidomide: 15 mg orally on days 1-21 (omitted on days 1,8,15 - days of bortezomib) 1, 5
Dexamethasone: 20 mg on day of and day after bortezomib 1, 5
35-day cycle 5
Efficacy of VRD-lite: 5
- Overall response rate: 86%
- VGPR or better: 66%
- Median PFS: 35.1 months
Treatment Duration and Sequencing
For transplant-eligible patients: 1
- Four to six courses of VRD induction are recommended before proceeding to stem cell collection
- VRD is widely used in the United States and becoming standard of care in Europe
For transplant-ineligible patients: 1
- VRD followed by maintenance therapy with lenalidomide/dexamethasone until progression or unacceptable toxicity
Special Considerations
High-Risk vs Standard-Risk Disease
VRD shows differential outcomes based on risk stratification: 3
- Standard-risk patients: median PFS 76.5 months; 10-year OS 58%
- High-risk patients: median PFS 40.3 months; 10-year OS 29%
In high-risk patients, VMP (bortezomib, melphalan, prednisone) may have advantages over Rd-R (lenalidomide, dexamethasone followed by lenalidomide maintenance) 6
Renal Insufficiency
- For patients with acute renal insufficiency, bortezomib/cyclophosphamide/dexamethasone (CyBorD) may be preferred initially 1
- Consider switching to VRD after renal function improves 1
Common Adverse Events and Management
Peripheral neuropathy: more common with bortezomib (24% grade 3 with IV administration vs 5% without bortezomib) 1
- Use subcutaneous rather than IV administration of bortezomib to reduce neuropathy risk 1
- Consider dose reduction or schedule modification if neuropathy develops
Thromboembolic events:
- Prophylactic anticoagulation recommended with lenalidomide-containing regimens
Fatigue, hyperglycemia, and diarrhea are other common adverse events 4
Monitoring Response
- Response assessment should follow International Myeloma Working Group criteria 1
- Minimal residual disease (MRD) assessment increasingly important for evaluating depth of response 1
VRD represents a highly effective standard of care for multiple myeloma treatment, with robust evidence supporting its use in both transplant-eligible and ineligible patients.