Initial Treatment for Multiple Myeloma
For newly diagnosed symptomatic multiple myeloma, initiate treatment with the triplet regimen bortezomib-lenalidomide-dexamethasone (VRd), followed by autologous stem cell transplantation in eligible patients and lenalidomide maintenance until progression. 1, 2
Treatment Algorithm Based on Transplant Eligibility
Transplant-Eligible Patients (Age <65-70 years, Good Performance Status)
Induction Phase:
- Administer 4-6 cycles of VRd (bortezomib, lenalidomide 25 mg days 1-21, dexamethasone 40 mg weekly) as the preferred triplet regimen 2
- Use dexamethasone-based induction to avoid stem-cell damage from alkylating agents 3
- Peripheral blood progenitor cells should be collected as the stem cell source, not bone marrow 3, 2
Consolidation Phase:
- Proceed to high-dose melphalan 200 mg/m² IV with autologous stem cell transplantation (ASCT) 1, 2
- ASCT provides median progression-free survival of 50 months versus 36 months without transplant 2, 4
- This represents a 35% reduction in risk of disease progression or death (HR 0.65, p<0.001) 4
Maintenance Phase:
- Continue lenalidomide maintenance until disease progression for standard-risk patients 1, 2
- For high-risk cytogenetics (del17p, t(4;14), t(14;16), t(14;20)), use bortezomib-based maintenance instead of lenalidomide alone 1, 2, 5
Transplant-Ineligible Patients (Age >65-70 years, Significant Comorbidities, Poor Performance Status)
For Standard-Risk Disease:
- First-line option: Daratumumab-lenalidomide-dexamethasone (DRd) provides superior outcomes with median PFS of 61.9 months versus 34.4 months with lenalidomide-dexamethasone alone (44% reduction in progression risk, HR 0.56) 6, 7
- Alternative option: VRd remains effective with 92.9% overall response rate 6
- Meta-analysis demonstrates DRd reduces risk of progression or death by 40% compared to VRd (HR 0.60,95% CI 0.46-0.77) 7
For High-Risk Cytogenetics:
- Bortezomib-containing regimens (VRd or bortezomib-melphalan-prednisone) are preferred over lenalidomide-based therapy 8
- VMP reduces progression risk by 46% (HR 0.54) and death risk by 27% (HR 0.73) compared to Rd-R in high-risk patients 8
For Patients >75 Years with Standard-Risk Disease:
- Rd-R (lenalidomide-dexamethasone with lenalidomide maintenance) may be better tolerated than VMP 8
- Continue therapy until progression rather than fixed-duration treatment 5
Essential Supportive Care Measures
Thromboprophylaxis (Critical):
- All patients on immunomodulatory drugs (lenalidomide) require full-dose aspirin or therapeutic anticoagulation 2, 5
Infection Prophylaxis:
- Herpes zoster prophylaxis with acyclovir or valacyclovir for all patients on proteasome inhibitors (bortezomib) 2, 5
- Use subcutaneous bortezomib for patients with pre-existing or high-risk peripheral neuropathy 5
- Pneumocystis jiroveci prophylaxis for patients receiving high-dose glucocorticosteroids 2
Skeletal Protection:
- Administer bisphosphonates to reduce skeletal-related events 1
Response Monitoring
Frequency:
- Assess response with each treatment cycle using serum and urine protein electrophoresis plus serum free light chains 2, 5
- Once best response achieved or on maintenance, assess at minimum every 3 months 2, 5
Complete Response Criteria:
- <5% plasma cells in bone marrow and negative immunofixation 1, 2
- MRD negativity rate with DRd is 24.2% versus 7.3% with Rd alone (p<0.0001) 6
Critical Pitfalls to Avoid
Do not use melphalan-prednisone alone in 2025:
- The 2008 guidelines recommended melphalan-prednisone for elderly patients 3, but this has been superseded by novel agent-based triplet regimens that provide dramatically superior outcomes 1, 2
Do not use lenalidomide-based regimens in lenalidomide-refractory patients:
- Switch to proteasome inhibitor with monoclonal antibody combinations 2
Do not use single or doublet therapy when triplet combinations are tolerated:
- Triplet regimens consistently demonstrate superior outcomes across all patient populations 2
Do not overlook cytogenetic risk stratification: