What is the recommended treatment regimen for multiple myeloma?

Multiple Myeloma Treatment Regimens

For newly diagnosed multiple myeloma patients, triplet therapy with bortezomib, lenalidomide, and dexamethasone (VRd) is the standard first-line treatment, with treatment selection further refined based on transplant eligibility and risk stratification. 1

Treatment Algorithm Based on Patient Characteristics

Transplant-Eligible Patients

1. Induction Therapy:

   • Standard Risk: VRd (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) for 3-4 cycles 1, 2
   • High-Risk: Consider daratumumab-VRd (D-VRd) for patients with high-risk cytogenetic abnormalities 1, 3

2. Stem Cell Collection and Transplantation:

   • Proceed to autologous stem cell transplantation (ASCT) after induction 3, 1
   • Consider harvesting peripheral blood stem cells prior to prolonged exposure to lenalidomide 3
   • High-dose melphalan (200 mg/m²) is the standard conditioning regimen 1

3. Maintenance Therapy:

   • Standard Risk: Lenalidomide until progression 1, 3
   • High-Risk: Bortezomib plus lenalidomide maintenance 1, 2

Transplant-Ineligible Patients

1. Primary Treatment Options:

   • VRd for approximately 8-12 cycles followed by maintenance 2
   • Daratumumab-lenalidomide-dexamethasone (DRd) until progression 3, 1
   • Alternative regimens: VMP (bortezomib, melphalan, prednisone) for 9 cycles 1

2. Maintenance Therapy:

   • Continuous therapy with lenalidomide until progression 3

Relapsed/Refractory Disease

Triplet therapy including a monoclonal antibody with an immunomodulatory drug and/or proteasome inhibitor is recommended for relapsed disease. 3

Treatment selection depends on:

• Prior therapies and response
• Duration of response to previous treatment
• Refractory status (single, dual, or triple refractory) 3

Preferred Regimens for Relapsed Disease:

1. IMiD Refractory: Daratumumab-bortezomib-dexamethasone (DVd) 3, 4
2. PI Refractory: Daratumumab-lenalidomide-dexamethasone (DRd) 3, 4
3. Dual Refractory (lenalidomide and bortezomib): Daratumumab-pomalidomide-dexamethasone (DPd) 3
4. Consider ASCT if not received previously or if progression-free survival after first transplant was ≥18 months 3

Important Supportive Care Measures

• Herpes zoster prophylaxis for patients treated with proteasome inhibitors 3, 1
• Subcutaneous bortezomib preferred over IV administration to reduce peripheral neuropathy risk 3, 1, 5
• Prophylactic anticoagulation for patients receiving immunomodulatory-based therapy 3, 1
• Monitor for secondary malignancies with long-term lenalidomide maintenance 3

Response Assessment

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

Special Considerations

• High-risk features include cytogenetic abnormalities such as del(17p), t(4;14), t(14;16), t(14;20), and gain(1q) 1, 2
• Elderly or frail patients may require dose reductions (e.g., reduced dexamethasone 8-20 mg weekly for patients >75 years) 1
• Consider VRd lite (modified dosing schedule) for patients who cannot tolerate standard VRd 6
• Limit exposure to myelotoxic agents in transplant candidates to preserve stem cell reserve 3

By following this treatment algorithm based on patient characteristics and disease status, clinicians can optimize outcomes for multiple myeloma patients while managing potential toxicities.