What is the recommended initial treatment regimen for multiple myeloma?

Initial Treatment Regimens for Multiple Myeloma

For newly diagnosed multiple myeloma patients, a triplet regimen containing bortezomib is the recommended initial treatment, with specific regimens determined by transplant eligibility. 1, 2

Treatment Algorithm Based on Transplant Eligibility

Transplant-Eligible Patients (typically <65 years or fit patients)

1. Induction Therapy (3-4 cycles)

   • First choice: VRd (bortezomib, lenalidomide, dexamethasone) 2, 3
   • Alternative for high-risk patients: Daratumumab-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) 2, 3
   • Other effective options: VTD (bortezomib, thalidomide, dexamethasone) or VCD (bortezomib, cyclophosphamide, dexamethasone) 1

2. Stem Cell Collection and Transplantation

   • High-dose melphalan (200 mg/m²) followed by ASCT 1, 2
   • Peripheral blood progenitor cells are preferred over bone marrow 1

3. Maintenance

   • Standard-risk patients: Lenalidomide until progression 1, 2
   • High-risk patients: Bortezomib plus lenalidomide 1, 2

Transplant-Ineligible Patients (typically ≥65 years or unfit patients)

1. Initial Treatment

   • First choice: VMP (bortezomib, melphalan, prednisone) or MPT (melphalan, prednisone, thalidomide) 1
   • Alternative: Rd (lenalidomide, low-dose dexamethasone) continuously until progression 1
   • For high-risk patients: Daratumumab-VMP 2

2. Duration

   • Fixed duration for VMP/MPT (typically 9 cycles for VMP) 1
   • Continuous therapy until progression for Rd 1

Risk Stratification

Risk stratification is essential before initiating treatment:

• High-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain(1q), or p53 mutation 2, 3
• Standard-risk: absence of high-risk cytogenetic abnormalities 2

Considerations for Specific Regimens

VRd (Bortezomib, Lenalidomide, Dexamethasone)

• Dosing: Bortezomib 1.3 mg/m² subcutaneously days 1,8,15; lenalidomide 25 mg orally days 1-14; dexamethasone 20 mg on day of and day after bortezomib (or 40 mg days 1,8,15,22) 1
• Cycle length: 21 days
• Advantages: High response rates, improved progression-free survival

VMP (Bortezomib, Melphalan, Prednisone)

• Dosing: Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22; melphalan 9 mg/m² orally days 1-4; prednisone 60 mg/m² orally days 1-4 1
• Cycle length: 35 days
• Advantages: Well-established efficacy in elderly patients

Rd (Lenalidomide, Low-dose Dexamethasone)

• Dosing: Lenalidomide 25 mg orally days 1-21; dexamethasone 40 mg orally days 1,8,15,22 1
• Cycle length: 28 days
• Advantages: Oral administration, well-tolerated in elderly patients

Important Considerations and Pitfalls

• Subcutaneous bortezomib is preferred over intravenous administration to reduce peripheral neuropathy risk 1, 2
• Thromboprophylaxis is mandatory with immunomodulatory drugs (lenalidomide, thalidomide) 2
• Dose adjustments are necessary for elderly (>75 years) or frail patients 2
• Avoid alkylating agents during induction in transplant-eligible patients to prevent stem cell damage 2
• Herpes zoster prophylaxis is recommended for patients on proteasome inhibitors (bortezomib) 1
• Monitor for common complications: peripheral neuropathy, cytopenias, infections, and thrombotic events 2

Response Assessment

• Evaluate response after each cycle during induction
• Once best response is achieved, monitor every 3 months
• Response criteria include complete response (CR), very good partial response (VGPR), and partial response (PR) 1

Triplet regimens are superior to doublet regimens in terms of response rates and progression-free survival, with the exception of very elderly or frail patients who may benefit from less intensive therapy 2.