What is the recommended treatment regimen for managing multiple myeloma?

Multiple Myeloma Management

The recommended treatment regimen for multiple myeloma should be stratified based on transplant eligibility, with triplet regimens containing bortezomib as the standard of care for initial treatment in most patients. 1

Initial Treatment Approach

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

1. Induction Therapy

   • First choice: VRd (bortezomib, lenalidomide, dexamethasone) for 3-4 cycles 1, 2
   • Alternative options:
     • VTD (bortezomib, thalidomide, dexamethasone)
     • VCD (bortezomib, cyclophosphamide, dexamethasone)
     • PAD (bortezomib, doxorubicin, dexamethasone) 3, 1
   • For high-risk patients: D-VRd (daratumumab, bortezomib, lenalidomide, dexamethasone) 1, 2

2. Stem Cell Collection and Transplantation

   • High-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation (ASCT) 3, 1
   • Peripheral blood progenitor cells are preferred over bone marrow 3, 1
   • Tandem ASCT may benefit patients not achieving very good partial response after first ASCT 3

3. Maintenance Therapy

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

Transplant-Ineligible Patients (>65 years or unfit patients)

1. First-line Treatment Options:

   • First choice: VMP (bortezomib, melphalan, prednisone) for 9 cycles 3, 1
   • Alternative: MPT (melphalan, prednisone, thalidomide) 3
   • Other option: Rd (lenalidomide, low-dose dexamethasone) continuously until progression 1
   • For patients with neuropathy at diagnosis: Bendamustine plus prednisone 3

2. Duration of Treatment:

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

Management of Relapsed/Refractory Disease

1. First Relapse:

   • Preferred approach: Triplet regimens including a monoclonal antibody with an immunomodulatory drug and/or proteasome inhibitor 3
   • Consider prior therapies when selecting treatment - patients relapsing >1 year after previous therapy may respond to the same regimen 3
   • Daratumumab-based combinations show superior outcomes 3, 4

2. Specific Regimens:

   • Daratumumab, lenalidomide, and dexamethasone (DRd) 3, 4
   • Daratumumab, bortezomib, and dexamethasone (DVd) 4
   • Carfilzomib, lenalidomide, and dexamethasone 3
   • Bendamustine-based combinations (BRd) for heavily pretreated patients 5, 6

3. Transplant Consideration:

   • ASCT should be offered to transplant-eligible patients who did not receive it as part of initial therapy 3
   • Repeat ASCT may be considered if progression-free survival after first transplant was ≥18 months 3

Special Considerations

High-Risk Disease

• High-risk features: del(17p), t(4;14), t(14;16), t(14;20), gain(1q), or p53 mutation 1, 2
• More aggressive treatment approach with triplet or quadruplet regimens 1
• Consider early use of daratumumab-containing regimens 1, 4

Elderly or Frail Patients

• Dose modifications may be required:
  • Reduced dexamethasone (8-20 mg weekly for patients >75 years) 1
  • Bortezomib-based regimens preferred for patients with renal impairment (no dose adjustment needed) 1

Supportive Care

• Bisphosphonates to reduce skeletal events 3
• Herpes zoster prophylaxis for patients on proteasome inhibitors 1
• Anticoagulation prophylaxis for patients on immunomodulatory drugs, especially those with high tumor burden or history of thrombosis 3

Monitoring Response

• Evaluate response after each cycle during induction 1
• Once best response is achieved, monitor every 3 months 1
• Response assessment based on serum and urine electrophoresis 3
• Complete response requires bone marrow aspiration (<5% plasma cells) and negative immunofixation 3

Common Pitfalls to Avoid

• Delaying transplant evaluation in eligible patients
• Using fixed-duration therapy instead of continuous therapy when the latter is indicated
• Overlooking cytogenetic risk stratification
• Failing to adjust doses for elderly or frail patients
• Not monitoring for common complications (renal dysfunction, hypercalcemia, bone disease) 1