What is the initial treatment approach for multiple myeloma?

Initial Treatment Approach for Multiple Myeloma

For newly diagnosed multiple myeloma, a triplet regimen consisting of bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT) in eligible patients, and maintenance therapy with lenalidomide until disease progression is the standard first-line treatment approach. 1

Risk-Stratified Induction Therapy

Standard-Risk Patients:

• VRd (bortezomib, lenalidomide, dexamethasone) is the standard induction regimen with complete response rates of 33-44% 1
• Typically administered for 3-6 cycles before proceeding to transplant 1

High-Risk Patients:

• D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) is preferred due to superior progression-free survival (84.3% vs 67.7% at 48 months) compared to VRd alone 1
• High-risk features include cytogenetic abnormalities (t(4;14), del(17p), t(14;16)), early relapse post-transplant, and high plasma cell labeling index (PCLI ≥3%) 1

Transplant-Ineligible Patients:

• DRd (daratumumab, lenalidomide, dexamethasone) shows superior outcomes with 44% reduction in risk of disease progression or death compared to Rd (lenalidomide, dexamethasone) 2
• After median follow-up of 64 months, median PFS was 61.9 months with DRd vs 34.4 months with Rd 2
• Recent meta-analysis shows lower risk of disease progression or death with DRd versus VRd (HR: 0.56; 95% CI: 0.39,0.82) 3

Autologous Stem Cell Transplantation (ASCT)

• ASCT should be offered to all eligible patients as it remains the standard of care 1
• Significantly improves progression-free survival compared to continued RVD alone (50 months vs 36 months) 4
• Stem cell collection should be performed early, especially with lenalidomide-based regimens (after 4-6 cycles) 1
• Consider tandem ASCT if not achieving VGPR after first transplant, particularly for patients with high-risk cytogenetics 1

Maintenance Therapy

• Lenalidomide maintenance until disease progression is the standard approach 1
• Provides almost 2-fold advantage in progression-free survival 1
• Consider bortezomib-based maintenance for high-risk patients 1

Response Assessment

• 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
• Partial response (PR): ≥50% reduction of M-gradient in serum, ≥90% reduction in 24-h urine 1
• Minimal residual disease (MRD) assessment is increasingly used to evaluate treatment efficacy 1

Supportive Care Measures

• Bisphosphonates with calcium and vitamin D supplementation 1
• Pneumocystis jiroveci prophylaxis for patients on high-dose steroids 1
• Herpes zoster prophylaxis for patients receiving proteasome inhibitors 1
• Antithrombotic prophylaxis for patients on immunomodulators 1
• Subcutaneous bortezomib preferred over intravenous to reduce peripheral neuropathy risk 1

Special Considerations

• For frail or elderly patients (>75 years), use reduced-dose regimens with dexamethasone 8-20 mg weekly 1
• Lenalidomide dose should be based on creatinine clearance 1
• Bortezomib does not require dose adjustment for renal impairment 1

Common Pitfalls to Avoid

• Delaying transplant evaluation in eligible patients
• Using fixed-duration therapy instead of continuous therapy
• Overlooking cytogenetic risk stratification
• Failing to adjust doses for elderly or frail patients
• Not monitoring for common complications and second primary malignancies
• Neglecting supportive care measures 1