What is the initial treatment approach for multiple myeloma?

Initial Treatment for Multiple Myeloma

For newly diagnosed symptomatic multiple myeloma, initiate treatment with the triplet regimen bortezomib, lenalidomide, and dexamethasone (VRd), followed by autologous stem cell transplantation in eligible patients and lenalidomide maintenance therapy until progression. 1, 2

Treatment Algorithm Based on Transplant Eligibility

Transplant-Eligible Patients (Age <65 years, Good Performance Status)

Induction Phase:

• Administer 4-6 cycles of VRd (bortezomib, lenalidomide, dexamethasone) as the preferred triplet regimen 2
• Use dexamethasone-based induction to avoid stem-cell damage from alkylating agents 3
• Assess response with each treatment cycle using serum and urine protein electrophoresis 2

Consolidation Phase:

• Proceed to high-dose melphalan 200 mg/m² intravenously with autologous stem cell transplantation (ASCT) 3, 2
• Use peripheral blood progenitor cells as the stem cell source rather than bone marrow 3, 2
• This approach provides median progression-free survival of 50 months versus 36 months with delayed transplant 2, 4

Maintenance Phase:

• Continue lenalidomide maintenance therapy until disease progression 1, 2
• For high-risk cytogenetics (del 17p, t(4;14), t(14;16), t(14;20)), consider bortezomib-based maintenance instead 1, 5

Transplant-Ineligible Patients (Age >65 years or Significant Comorbidities)

Primary Treatment Options:

Preferred Regimen:

• Daratumumab, lenalidomide, and dexamethasone (DRd) is now the preferred option for transplant-ineligible patients 6, 7
• The MAIA trial demonstrated median PFS of 61.9 months with DRd versus 34.4 months with lenalidomide-dexamethasone alone (44% reduction in risk of disease progression or death) 6
• Overall response rate of 92.9% with DRd, including 47.6% achieving complete response or better 6
• Meta-analysis shows DRd has lower risk of disease progression or death compared to VRd (HR 0.60; 95% CI: 0.46,0.77) 7

Alternative Regimen:

• VRd (bortezomib, lenalidomide, dexamethasone) remains an acceptable alternative 1, 5
• Continue therapy until disease progression rather than fixed-duration treatment 5

Historical Standard (Now Superseded):

• Melphalan-prednisone with thalidomide was previously standard but has been replaced by novel agent combinations 3

Risk-Stratified Modifications

Standard Risk Patients:

• VRd induction followed by ASCT (if eligible) and lenalidomide maintenance 1

High-Risk Cytogenetics (del 17p, t(4;14), t(14;16), t(14;20)):

• VRd induction followed by ASCT (if eligible) 1
• Critical: Use bortezomib-based maintenance therapy rather than lenalidomide alone for high-risk patients 1, 2

Essential Supportive Care Measures

Thromboprophylaxis (Mandatory):

• All patients receiving immunomodulatory drugs (lenalidomide, pomalidomide, thalidomide) require thromboprophylaxis 1, 2, 5
• Use full-dose aspirin or therapeutic anticoagulation 2, 5

Infection Prophylaxis:

• Herpes zoster prophylaxis with acyclovir or valacyclovir for all patients on proteasome inhibitors (bortezomib) 2, 5
• Pneumocystis jiroveci prophylaxis for patients receiving high-dose glucocorticosteroids 2

Bone Protection:

• Administer bisphosphonates to reduce skeletal-related events 1

Neuropathy Prevention:

• Use subcutaneous bortezomib (rather than intravenous) for patients with pre-existing or high-risk peripheral neuropathy 5

Response Monitoring Protocol

During Active Treatment:

• Assess response with each treatment cycle using serum and urine protein electrophoresis and serum free light chains 2, 5
• Complete response requires <5% plasma cells in bone marrow and negative immunofixation 1, 2

During Maintenance:

• Once best response achieved, assess at minimum every 3 months 2, 5
• Use whole-body low-dose CT rather than conventional skeletal survey for bone assessment 1, 5

Critical Pitfalls to Avoid

Do not observe asymptomatic/Stage I myeloma: Immediate treatment is not recommended for patients with indolent myeloma 3

Do not use single or doublet therapy when triplet combinations are tolerated: Triplet regimens consistently demonstrate superior outcomes 2

Do not use alkylating agents during induction in transplant-eligible patients: This causes stem-cell damage and compromises subsequent transplant 3

Do not overlook high-risk cytogenetics: These patients require intensified therapy with bortezomib-based maintenance rather than lenalidomide alone 2, 5

Do not delay frailty assessment: Frail patients experience higher rates of treatment discontinuation and non-hematologic toxicity, requiring dose modifications 1