Treatment of Multiple Myeloma

Initial Treatment for Newly Diagnosed Disease

The American College of Cardiology is not applicable here, however, for transplant-eligible patients, induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) followed by autologous stem cell transplantation (ASCT) and continuous lenalidomide maintenance until progression is the standard of care 1, 2
For transplant-eligible patients, the International Myeloma Society recommends administering 4-6 cycles of VRd (bortezomib, lenalidomide, dexamethasone) as the preferred triplet regimen 1
High-dose melphalan (200 mg/m²) with ASCT using peripheral blood progenitor cells as the preferred stem cell source is recommended by the European Society for Medical Oncology 1, 2
ASCT provides median progression-free survival of 50 months versus 36 months with delayed transplant, according to the National Comprehensive Cancer Network 3

For first relapse, triplet therapy with daratumumab-lenalidomide-dexamethasone (DRd) is the preferred option based on superior efficacy across all cytogenetic risk groups, as recommended by the International Myeloma Society 3, 1
The European Society for Medical Oncology recommends lenalidomide-sensitive patients receive DRd, which provides 91.3% overall response rate and median PFS of 45.0 months, although the exact reference is not provided, an alternative is carfilzomib-lenalidomide-dexamethasone (KRd) 5
For lenalidomide-refractory patients, the National Comprehensive Cancer Network suggests daratumumab-bortezomib-dexamethasone (DVd) 5, 1

The American Society of Clinical Oncology recommends all patients require comprehensive supportive care to prevent treatment-related complications, including thromboprophylaxis with full-dose aspirin or therapeutic anticoagulation for all patients on immunomodulatory drugs (lenalidomide, pomalidomide, thalidomide) 1, 4
Herpes zoster prophylaxis with acyclovir or valacyclovir for all patients on proteasome inhibitors is recommended by the Infectious Diseases Society of America 6, 1, 4
Pneumocystis jiroveci prophylaxis for patients receiving high-dose glucocorticosteroids is recommended by the Centers for Disease Control and Prevention 6, 7

The International Myeloma Society recommends assessing response with each treatment cycle using serum and urine protein electrophoresis and serum free light chains 1, 4
Once best response achieved or on maintenance, the European Society for Medical Oncology suggests assessing at minimum every 3 months 4
Complete response requires <5% plasma cells in bone marrow and negative immunofixation, as defined by the National Comprehensive Cancer Network 2

The National Comprehensive Cancer Network recommends not using lenalidomide-based regimens in patients progressing on lenalidomide maintenance—switch to proteasome inhibitor with monoclonal antibody 3
The American Society of Clinical Oncology suggests not delaying restaging at relapse—evaluation for disease evolution to plasma cell leukemia or extramedullary disease is critical as treatment approach differs dramatically 5, 7
The European Society for Medical Oncology recommends not using single or doublet therapy when triplet combinations are tolerated—triplet regimens consistently demonstrate superior outcomes 5, 3
The International Myeloma Society suggests not overlooking high-risk cytogenetics—these patients require intensified therapy with bortezomib-based maintenance rather than lenalidomide alone 1, 4