What is the typical treatment regimen for multiple myeloma?

Treatment Regimen for Multiple Myeloma

The standard treatment for multiple myeloma consists of a triplet regimen with bortezomib, lenalidomide, and dexamethasone (VRd) for induction, followed by autologous stem cell transplantation (ASCT) in eligible patients, and maintenance therapy with lenalidomide until progression. 1, 2

Initial Risk Stratification

• Multiple myeloma diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma plus evidence of CRAB features (hypercalcemia, renal failure, anemia, or lytic bone lesions) or other myeloma defining events 2
• Risk stratification is essential using cytogenetic analysis to identify high-risk features such as del(17p), t(4;14), t(14;16), t(14;20), or gain 1q 2
• The International Staging System (ISS) combines β2-microglobulin and albumin levels to assess prognosis 3, 4

Treatment Approach Based on Transplant Eligibility

Transplant-Eligible Patients (<65 years)

• Induction therapy: Bortezomib, lenalidomide, and dexamethasone (VRd) for 3-4 cycles 3, 1, 2
• For high-risk patients, daratumumab combined with VRd (Dara-VRd) is an alternative 2
• Stem cell collection: Peripheral blood progenitor cells are preferred over bone marrow 3
• Conditioning regimen: High-dose melphalan (200 mg/m²) followed by ASCT 3, 1
• Consolidation: Two additional cycles of VRd post-transplant 5
• Maintenance therapy: Lenalidomide until progression for standard-risk patients; bortezomib plus lenalidomide for high-risk patients 2, 3

Transplant-Ineligible Patients (>65 years)

• Induction therapy: VRd for 8-12 cycles or daratumumab, lenalidomide, dexamethasone (DRd) until progression 2
• Alternatively, melphalan-prednisone-based regimens with novel agents (bortezomib, lenalidomide) 3
• Maintenance therapy: Continuous therapy with lenalidomide until progression 3, 6

Response Assessment

• Evaluate response with each treatment cycle using serum and urine electrophoresis 3
• Complete response requires <5% plasma cells in bone marrow and negative immunofixation 3
• Minimal residual disease (MRD) testing can help guide treatment decisions 5

Treatment of Relapsed/Refractory Disease

• First relapse options (lenalidomide-sensitive):

  • Daratumumab, lenalidomide, dexamethasone (DRd) - preferred option 3, 7
  • Carfilzomib, lenalidomide, dexamethasone (KRd) 3
  • Ixazomib, lenalidomide, dexamethasone (IRd) 3

• First relapse options (lenalidomide-refractory):

  • Daratumumab, bortezomib, dexamethasone (DVd) - preferred option 3, 7
  • Carfilzomib, pomalidomide, dexamethasone (KPd) 3
  • Pomalidomide-based combinations 3

• Second or higher relapse:

  • Consider regimens with at least 2 new drugs that the patient is not refractory to 3
  • Options include quadruplet regimens, selinexor-based regimens, bendamustine-based regimens, or venetoclax for t(11;14) myeloma 3

Supportive Care

• Bisphosphonates should be administered to reduce skeletal-related events 3
• Thromboprophylaxis for patients on immunomodulatory drugs 3
• Herpes zoster prophylaxis for patients on proteasome inhibitors 3

Common Pitfalls and Caveats

• Triplet regimens are standard but may need dose adjustments for elderly or frail patients 3
• Subcutaneous bortezomib is preferred over intravenous administration to reduce peripheral neuropathy risk 3, 8
• Lenalidomide maintenance after transplant carries an increased risk of secondary cancers; benefits versus risks should be discussed with patients 3
• Continuous therapy has shown superior outcomes compared to fixed-duration therapy in multiple trials 3
• Avoid prolonged exposure to alkylating agents before stem cell collection to preserve stem cell reserve 3