What is the approach to prognostication and treatment of multiple myeloma?

Prognostication and Treatment of Multiple Myeloma

The approach to prognostication in multiple myeloma should utilize the Revised International Staging System (R-ISS) which incorporates cytogenetic abnormalities along with biochemical markers to guide risk-adapted treatment strategies. 1

Prognostic Assessment

Staging Systems

• Durie-Salmon Classification: Traditionally used system based on hemoglobin, calcium, M-protein levels, bone lesions, and renal function 2
• International Staging System (ISS): Based on serum β2-microglobulin and albumin levels 2
• Revised International Staging System (R-ISS): Currently recommended approach that combines:
  • ISS staging
  • Cytogenetic abnormalities
  • Serum lactate dehydrogenase (LDH) levels 1

High-Risk Cytogenetic Features

• del(17p)
• t(4;14)
• t(14;16)
• t(14;20)
• gain(1q) 1

These cytogenetic abnormalities are critical for risk stratification and should be obtained either by conventional karyotyping or FISH analysis 2.

Additional Prognostic Factors

• Early relapse post-transplant or initial therapy
• High plasma cell labeling index (PCLI ≥3%)
• Renal dysfunction
• Elevated LDH
• Extensive bone disease 1, 3

Risk-Stratified Treatment Approach

Asymptomatic/Smoldering Myeloma

• Immediate treatment is not recommended for patients with indolent myeloma 2
• Regular monitoring is essential to detect progression to symptomatic disease 4

Newly Diagnosed Symptomatic Multiple Myeloma

Transplant-Eligible Patients (<65 years)

1. Induction Therapy:

   • VRd (bortezomib, lenalidomide, dexamethasone) is the standard first-line therapy 1, 3
   • For high-risk patients, consider Daratumumab-VRd 1, 5

2. Consolidation:

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

3. Maintenance Therapy:

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

Transplant-Ineligible Patients (>65 years)

1. Standard Treatment Options:

   • Melphalan plus prednisone with thalidomide has shown superiority over melphalan-prednisone alone 2
   • VRd (bortezomib, lenalidomide, dexamethasone) in reduced doses for elderly patients 1
   • Dose adjustments are critical: reduced-dose dexamethasone (8-20 mg weekly) for patients >75 years 1

2. Maintenance Therapy:

   • Lenalidomide or bortezomib-based maintenance depending on risk status 1

Response Evaluation

Response Criteria

• Complete Response (CR): Negative serum/urine immunofixation and <5% plasma cells in bone marrow 1
• Very Good Partial Response (VGPR): ≥90% reduction in serum M-protein 1
• Partial Response (PR): ≥50% reduction in serum M-protein and ≥90% reduction in 24-h urine M-protein 1

Monitoring Schedule

• Evaluate response after each cycle during induction
• Once best response is achieved, monitor every 3 months 1

Supportive Care

• Bone Disease: Bisphosphonates to reduce skeletal-related events 2, 1
• Thrombosis Prevention: Anticoagulation prophylaxis for patients on immunomodulatory drugs 1
• Infection Prevention: Herpes zoster prophylaxis for patients on proteasome inhibitors 1

Common Pitfalls to Avoid

1. Delaying transplant evaluation in eligible patients
2. Overlooking cytogenetic risk stratification which is essential for treatment planning
3. Failing to adjust doses for elderly or frail patients
4. Not monitoring for common complications such as renal dysfunction, hypercalcemia, and bone disease 1
5. Using fixed-duration therapy instead of continuous therapy in appropriate patients 1

Treatment of Relapsed/Refractory Disease

For relapses occurring after unmaintained remission, regimens similar to those used initially can induce a second remission. For patients who fail initial treatment with alkylating agents, VAD (vincristine, adriamycin, dexamethasone) is a standard option 2.

Novel agents such as thalidomide, bortezomib, and lenalidomide have shown efficacy in relapsed/refractory settings 2, 6.