What is the recommended treatment for multiple myeloma?

Multiple Myeloma Treatment Recommendations

The recommended treatment for multiple myeloma follows a risk-adapted approach with combination therapies including proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and stem cell transplantation for eligible patients to optimize survival outcomes. 1

Initial Treatment Approach Based on Transplant Eligibility

Transplant-Eligible Patients

1. Induction Therapy:

   • Preferred regimen: D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) - superior progression-free survival (84.3% vs 67.7% at 48 months) compared to VRd alone 1
   • Standard regimen: VRd (bortezomib, lenalidomide, dexamethasone) 1, 2
   • Typically administered for 3-4 cycles before proceeding to transplant 1

2. Stem Cell Collection:

   • Perform early, especially with lenalidomide-based regimens (after 4-6 cycles) 1
   • Limit exposure to myelotoxic agents (including alkylating agents and nitrosoureas) to avoid compromising stem cell reserve 3

3. Autologous Stem Cell Transplantation (ASCT):

   • Standard preparative regimen: Melphalan 200 mg/m² IV 3
   • Peripheral blood progenitor cells preferred over bone marrow 3
   • Consider tandem ASCT if not achieving VGPR after first transplant, particularly for high-risk cytogenetics 1

4. Maintenance Therapy:

   • Standard risk: Lenalidomide until disease progression 1
   • 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
   • DRd (daratumumab, lenalidomide, dexamethasone) until progression 2
   • Alternative regimens: Melphalan/prednisone (MP), bortezomib/melphalan/prednisone (VMP) 3

2. Maintenance Therapy:

   • Lenalidomide until disease progression 1

Treatment of Relapsed/Refractory Disease

1. First Relapse:

   • For lenalidomide-naïve patients: DRd (daratumumab, lenalidomide, dexamethasone) 1
   • For lenalidomide-refractory patients: DVd (daratumumab, bortezomib, dexamethasone) or KPd (carfilzomib, pomalidomide, dexamethasone) 1
   • For bortezomib-refractory patients: DRd or KRd (carfilzomib, lenalidomide, dexamethasone) 1

2. Later Relapses:

   • Pomalidomide plus low-dose dexamethasone - shown superior progression-free survival compared to high-dose dexamethasone (4.0 months vs 1.9 months) 4
   • Elotuzumab in combination with lenalidomide and dexamethasone for patients who have received 1-3 prior therapies 5
   • Elotuzumab with pomalidomide and dexamethasone for patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor 5

Supportive Care Measures

1. Bone Health:

   • Bisphosphonates with calcium and vitamin D supplementation 1

2. Infection Prevention:

   • Herpes zoster prophylaxis for patients on proteasome inhibitors 3, 1
   • Pneumocystis jiroveci prophylaxis for patients on high-dose steroids 1
   • Seasonal influenza and pneumococcal vaccinations 1

3. Thrombosis Prevention:

   • Prophylactic anticoagulation for patients on immunomodulatory therapy 3, 1

4. Peripheral Neuropathy Management:

   • Consider subcutaneous bortezomib instead of IV to reduce peripheral neuropathy risk 3, 1

Monitoring and 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 3, 1
• Regular monitoring: Full blood count, serum and urine electrophoresis, free light chain determination, creatinine, calcium, and β2-microglobulin every 3-6 months 3, 1

Special Considerations

1. Elderly or Frail Patients:

   • Reduced-dose regimens with dexamethasone 8-20 mg weekly for patients >75 years 1
   • Lenalidomide dose based on creatinine clearance 1

2. High-Risk Features:

   • Cytogenetic abnormalities: del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation 2
   • Early relapse post-transplant or initial therapy 1
   • High plasma cell labeling index (PCLI ≥3%) 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 second primary malignancies
• Neglecting supportive care measures 1