What is the recommended treatment approach for multiple myeloma?

Treatment Approach for Multiple Myeloma

The recommended first-line treatment for multiple myeloma is a triplet regimen consisting of bortezomib, lenalidomide, and dexamethasone (VRd), followed by autologous stem cell transplantation (ASCT) in eligible patients, and maintenance therapy with lenalidomide until disease progression. 1, 2

Initial Treatment Approach

Risk Stratification

• Perform cytogenetic testing via FISH to identify high-risk features:
  • High-risk: del(17p), t(4;14), t(14;16), t(14;20), and gain(1q)
  • Early relapse post-transplant or initial therapy
  • High plasma cell labeling index (PCLI ≥3%)

Transplant-Eligible Patients (typically ≤65-70 years)

1. Induction Therapy:

   • VRd (bortezomib, lenalidomide, dexamethasone) for 3-4 cycles 2
   • For high-risk patients: Consider daratumumab-VRd 2
   • 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 2

2. Consolidation with ASCT:

   • High-dose melphalan (200 mg/m²) followed by ASCT 2, 3
   • Consider 2-3 additional cycles of VRd post-transplant 2

3. Maintenance Therapy:

   • Lenalidomide until progression or intolerance 1, 2
   • For high-risk patients: Consider bortezomib-based maintenance 2

Transplant-Ineligible Patients

1. Primary Treatment:

   • Triplet therapy recommended: VRd, daratumumab-VMP (bortezomib, melphalan, prednisone), or VMP 1, 2
   • For frail or elderly patients (>75 years): Consider Rd (lenalidomide, dexamethasone) 4
   • Dose adjustments based on age, renal function, comorbidities, and frailty status 1

2. Maintenance Therapy:

   • Continuous therapy recommended over fixed-duration therapy 1
   • Lenalidomide until progression is standard 2

Treatment of Relapsed Disease

First Relapse

• Immediate treatment for symptomatic relapse 1
• Triplet therapy preferred with two novel agents (PIs, immunomodulatory drugs, or monoclonal antibodies) 1
• Options based on prior therapy:
  • If lenalidomide-naïve: DRd (daratumumab, lenalidomide, dexamethasone) preferred 1, 5
  • If lenalidomide-refractory: DVd (daratumumab, bortezomib, dexamethasone) or KPd (carfilzomib, pomalidomide, dexamethasone) 1
  • Consider ASCT if not received previously or if ≥18 months since first transplant 1

Second or Higher Relapse

• Use combinations with at least 2 new drugs that the patient is not refractory to 1
• Consider:
  • Quadruplet regimens
  • Selinexor-based regimens
  • Panobinostat added to proteasome inhibitor regimens
  • Venetoclax for t(11;14) myeloma 1

Supportive Care

• Bisphosphonates to reduce skeletal-related events 2
• Antithrombotic prophylaxis for patients on immunomodulatory drugs 2
• Herpes zoster prophylaxis for patients on proteasome inhibitors 2
• Pain management for bone lesions 2

Treatment Response Evaluation

• Evaluate response after each cycle during induction 2
• Once best response is achieved, monitor every 3 months 2
• Response criteria:
  • Complete response (CR): negative serum/urine immunofixation, <5% plasma cells in bone marrow
  • Very good partial response (VGPR): ≥90% reduction in serum M-protein
  • Partial response (PR): ≥50% reduction in serum M-protein

Common Pitfalls to Avoid

1. Delaying transplant evaluation in eligible patients
2. Using fixed-duration therapy instead of continuous therapy
3. Overlooking cytogenetic risk stratification
4. Failing to adjust doses for elderly or frail patients
5. Not monitoring for common complications (renal dysfunction, hypercalcemia, bone disease)
6. Treating asymptomatic or smoldering myeloma prematurely 2

The treatment landscape for multiple myeloma continues to evolve rapidly with the introduction of novel agents. Triplet regimens incorporating proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have significantly improved outcomes 6. Treatment decisions should be guided by patient-specific factors including age, comorbidities, cytogenetic risk, and prior therapies.