What is the initial treatment approach for patients diagnosed with multiple myeloma?

Initial Treatment Approach for Multiple Myeloma

The initial treatment for multiple myeloma should include a triplet regimen consisting of bortezomib, lenalidomide, and dexamethasone (VRd) for both transplant-eligible and transplant-ineligible patients, followed by autologous stem cell transplantation (if eligible) and appropriate maintenance therapy. 1

Risk Stratification

Risk stratification is essential for guiding treatment decisions:

• Standard risk: Includes hyperdiploidy, t(11;14), t(6;14) 2
• Intermediate risk: Includes t(4;14), cytogenetic del 13, hypodiploidy 2
• High risk: Includes del(17p), t(14;16), t(14;20), high-risk gene expression profile 2, 3

Initial Treatment Based on Transplant Eligibility

Transplant-Eligible Patients

• Induction therapy: VRd (bortezomib, lenalidomide, dexamethasone) for 4-6 cycles 1, 3

  • Avoid prolonged induction (>4-6 cycles) to prevent difficulties with stem cell collection 3
  • For high-risk patients, bortezomib-based regimens are strongly preferred as they may overcome some adverse prognostic effects 3

• Consolidation: High-dose melphalan (200 mg/m²) followed by autologous stem cell transplantation 1

  • Peripheral blood progenitor cells are preferred over bone marrow as the stem cell source 1

• Maintenance therapy:

  • Standard-risk patients: Lenalidomide until progression 1
  • High-risk patients: Bortezomib-based maintenance therapy 1, 3

Transplant-Ineligible Patients

• Standard-risk patients:

  • VRd or lenalidomide plus dexamethasone (Rd) 3, 1
  • Daratumumab plus lenalidomide and dexamethasone (DRd) has shown superior progression-free survival compared to Rd (median PFS 61.9 vs 34.4 months) 4
  • Recent evidence suggests DRd may be superior to VRd in transplant-ineligible patients (HR 0.56; 95% CI: 0.39,0.82) 5

• High-risk patients:

  • Bortezomib-based triplet regimens are strongly recommended 3, 2
  • Treatment should be continued for approximately 12-18 months 6

Special Considerations

• Renal failure: Bortezomib-based regimens (VCd: bortezomib, cyclophosphamide, dexamethasone) are preferred due to non-renal clearance and rapid responses 3, 2

  • Avoid nephrotoxic drugs and maintain euvolemia 3
  • Bortezomib can be administered without dose adjustment in severe renal impairment and dialysis 2

• Response assessment:

  • Evaluate response with each treatment cycle using serum and urine electrophoresis 1
  • Complete response requires <5% plasma cells in bone marrow and negative immunofixation 1

Supportive Care

• Thromboprophylaxis is essential for patients on immunomodulatory drugs (lenalidomide) 1, 2

  • Aspirin for standard-risk patients
  • Low-molecular weight heparin, warfarin, or direct thrombin inhibitors for high-risk patients 2

• Bisphosphonates should be administered to reduce skeletal-related events 1

• Antimicrobial prophylaxis:

  • Herpes zoster prophylaxis for patients on proteasome inhibitors
  • Pneumocystis jirovecii prophylaxis for patients on dexamethasone
  • Levofloxacin during the first two cycles for newly diagnosed patients 2

Emerging Treatments

• Recent evidence shows that adding isatuximab to VRd significantly improves progression-free survival in transplant-ineligible patients (63.2% vs 45.2% at 60 months; HR 0.60) 7

• Daratumumab-based regimens have shown promising results with high response rates and improved survival outcomes 4

Common Pitfalls to Avoid

• Delaying treatment in patients with renal failure - prompt initiation of bortezomib-based therapy is crucial 2

• Neglecting risk stratification - treatment selection should be guided by cytogenetic risk factors 3, 2

• Prolonged induction therapy in transplant-eligible patients may impair stem cell collection 2

• Inadequate thromboprophylaxis in patients receiving immunomodulatory drugs can lead to serious complications 1, 2