Initial Treatment Approach for Multiple Myeloma
The recommended initial treatment for multiple myeloma is D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) as the preferred induction regimen, followed by autologous stem cell transplantation (ASCT) in eligible patients, and maintenance therapy with lenalidomide until disease progression. 1
Risk-Adapted Treatment Algorithm
Step 1: Initial Assessment and Risk Stratification
- Determine transplant eligibility (age, comorbidities, performance status)
- Assess cytogenetic risk profile (high-risk features include del(17p), t(4;14), t(14;16), and high plasma cell labeling index ≥3%)
- Evaluate renal function (for dose adjustments)
Step 2: Induction Therapy (3-6 cycles)
First choice: D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone)
- Superior progression-free survival (84.3% vs 67.7% at 48 months) compared to VRd alone 1
- Daratumumab 16 mg/kg IV combined with standard VRd regimen
Alternative: VRd (bortezomib, lenalidomide, dexamethasone)
- Standard triplet regimen with established efficacy 1
- Bortezomib 1.3 mg/m² (subcutaneous preferred over IV to reduce peripheral neuropathy)
- Lenalidomide 25 mg days 1-21 of 28-day cycle
- Dexamethasone 40 mg weekly (reduced to 20 mg for patients >75 years)
Step 3: Stem Cell Collection and Transplantation
- Collect stem cells early, especially with lenalidomide-based regimens (after 4-6 cycles) 1
- Proceed to ASCT in eligible patients
- ASCT significantly improves progression-free survival compared to continued RVd alone (50 months vs 36 months) 1
- Consider tandem ASCT if not achieving VGPR after first transplant, particularly for high-risk cytogenetics 1
Step 4: Consolidation (Optional)
- Consider 2-4 cycles of the original induction regimen post-ASCT
Step 5: Maintenance Therapy
- Lenalidomide maintenance until disease progression or intolerance 1
- Provides almost 2-fold advantage in progression-free survival 1
- For high-risk patients: Consider bortezomib-based maintenance 1
Special Considerations
Elderly or Frail Patients (>75 years)
- Reduce dexamethasone dose to 8-20 mg weekly 1
- Consider dose adjustments for other agents
- May not be eligible for ASCT
Renal Impairment
- Adjust lenalidomide dose based on creatinine clearance 1
- Bortezomib does not require dose adjustment for renal impairment 1
High-Risk Cytogenetics
- D-VRd strongly recommended over VRd 1
- Consider more intensive maintenance strategies
Supportive Care (Essential Components)
- Bone health: Bisphosphonates with calcium and vitamin D supplementation 1
- Infection prophylaxis:
- Pneumocystis jiroveci prophylaxis for patients on high-dose steroids
- Herpes zoster prophylaxis for patients on proteasome inhibitors
- Seasonal influenza and pneumococcal vaccinations 1
- Thromboprophylaxis: Antithrombotic prophylaxis for patients on immunomodulators 1
Response Assessment
- Monitor with full blood count, serum and urine electrophoresis, free light chain determination, creatinine, calcium, and β2-microglobulin every 3-6 months 1
- Complete response (CR): Negative serum/urine immunofixation and <5% plasma cells in bone marrow 1
- Very good partial response (VGPR): ≥90% reduction of serum M-component 1
- Consider minimal residual disease (MRD) assessment to evaluate treatment efficacy 1
Evidence from Clinical Trials
The CASSIOPEIA trial demonstrated that adding daratumumab to the VTd regimen (D-VTd) significantly improved stringent complete response rates (28.9% vs 20.3%, p=0.0010) and reduced the risk of progression or death by 53% compared to VTd alone (HR=0.47) 2. While this trial used thalidomide rather than lenalidomide, it supports the benefit of adding daratumumab to induction therapy.
Common Pitfalls to Avoid
- Delaying transplant evaluation in eligible patients 1
- Using fixed-duration therapy instead of continuous therapy 1
- Overlooking cytogenetic risk stratification 1
- Failing to adjust doses for elderly or frail patients 1
- Not providing appropriate supportive care (bisphosphonates, thromboprophylaxis, antiviral prophylaxis) 1
- Neglecting early stem cell collection with lenalidomide-based regimens 1
By following this risk-adapted approach with combination therapies including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and stem cell transplantation for eligible patients, outcomes for patients with multiple myeloma can be optimized.