What is the initial treatment for multiple myeloma?

Initial Treatment for Multiple Myeloma

The initial treatment for multiple myeloma should include a triplet regimen consisting of bortezomib, lenalidomide, and dexamethasone (VRd) for both transplant-eligible and transplant-ineligible patients. 1, 2

Treatment Approach Based on Transplant Eligibility

Transplant-Eligible Patients

• VRd (bortezomib, lenalidomide, dexamethasone) is the standard induction regimen for 3-4 cycles prior to stem cell collection 3
• Following induction, patients should proceed to high-dose melphalan (200 mg/m²) with autologous stem cell transplantation 1, 3
• Peripheral blood progenitor cells are preferred over bone marrow as the source of stem cells 1
• Post-transplant, patients should receive 2 additional cycles of VRd as consolidation 3
• Maintenance therapy with lenalidomide should be continued until progression 1, 3

Transplant-Ineligible Patients

• VRd (bortezomib, lenalidomide, dexamethasone) is recommended as the standard initial therapy 1, 2
• Alternative options include daratumumab plus bortezomib plus melphalan plus prednisone (D-VMP) 1, 4
• Continuous therapy until progression is preferred over fixed-duration therapy 1
• For very elderly or frail patients, dose adjustments should be made: dexamethasone 20mg weekly for patients >75 years, with further reduction to 8-20mg weekly for frail patients 1

Risk-Stratified Approach

Standard Risk Patients

• VRd induction followed by ASCT (if eligible) and lenalidomide maintenance 5
• For transplant-ineligible patients, continuous VRd or Rd (lenalidomide, dexamethasone) until progression 1

High-Risk Patients (del 17p, t(14;16), t(14;20))

• VRd induction followed by ASCT (if eligible) 5
• Bortezomib-based maintenance therapy is preferred over lenalidomide alone 1
• Consider proteasome inhibitor-based maintenance for at least 1 year 5

Response Assessment

• Response should be assessed with each treatment cycle using serum and urine electrophoresis 1
• Complete response requires <5% plasma cells in bone marrow and negative immunofixation 1
• Very good partial response is defined by ≥90% reduction in serum M-protein with positive immunofixation 1
• Partial response requires ≥50% reduction in serum M-protein and ≥90% reduction in 24-hour urine M-protein 1
• Whole-body low-dose CT is preferred over conventional skeletal survey for bone assessment 1

Common Pitfalls and Considerations

Renal Impairment

• Bortezomib-based regimens can be administered without dose adjustment in renal impairment 5
• Lenalidomide requires dose adjustment based on creatinine clearance 1
• For acute renal failure due to cast nephropathy, prompt initiation of bortezomib-based therapy is critical 5

Supportive Care

• Thromboprophylaxis is essential for patients on immunomodulatory drugs (lenalidomide) 5
• Herpes zoster prophylaxis should be given to all patients on proteasome inhibitors 5
• Bisphosphonates should be administered to reduce skeletal-related events 1

Treatment Duration

• Continuous therapy has shown superior outcomes compared to fixed-duration therapy in multiple trials 1
• The FIRST trial demonstrated improved progression-free survival and overall survival with continuous lenalidomide-dexamethasone compared to fixed-duration therapy 1
• Prolonged induction therapy (>4-6 cycles) in transplant-eligible patients may impair stem cell collection 5

The SWOG S0777 trial demonstrated that VRd significantly improved progression-free survival (43 months vs. 30 months) and overall survival (75 months vs. 64 months) compared to Rd alone in newly diagnosed multiple myeloma patients 2. This represents the strongest evidence supporting VRd as the standard initial treatment for multiple myeloma.