What are common chemotherapy regimens for a patient with multiple myeloma?

Common Chemotherapy Drugs and Regimens for Multiple Myeloma

The most commonly used chemotherapy drugs for multiple myeloma include bortezomib, lenalidomide, carfilzomib, cyclophosphamide, melphalan, and dexamethasone, typically used in combination regimens rather than as single agents. 1

Front-Line Therapy Regimens

For Transplant-Eligible Patients

Triplet regimens containing a proteasome inhibitor plus an immunomodulatory drug plus dexamethasone are the standard of care. 1, 2

Preferred regimens include:

• Bortezomib/lenalidomide/dexamethasone (VRd) - This remains the standard backbone for newly diagnosed multiple myeloma in transplant candidates 1, 3

  • Bortezomib 1.3 mg/m² subcutaneously days 1,8,15; lenalidomide 25 mg orally days 1-14; dexamethasone 20 mg on day of and day after bortezomib 1

• Bortezomib/cyclophosphamide/dexamethasone (VCD) 1

  • Cyclophosphamide 300 mg/m² orally days 1,8,15,22; bortezomib 1.3 mg/m² IV days 1,8,15,22; dexamethasone 40 mg orally days 1,8,15,22 1

• Bortezomib/thalidomide/dexamethasone (VTD) 1

  • Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22; thalidomide 100-200 mg orally days 1-21; dexamethasone 20 mg on day of and day after bortezomib 1

For Transplant-Ineligible Patients

Preferred regimens include:

• Lenalidomide/low-dose dexamethasone (Rd) - Category 1 recommendation 1

  • Lenalidomide 25 mg orally days 1-21; dexamethasone 40 mg orally days 1,8,15,22; repeated every 28 days, continued until progression 1, 4

• Bortezomib/melphalan/prednisone (VMP) 1

  • Bortezomib 1.3 mg/m² subcutaneously days 1,8,15,22; melphalan 9 mg/m² orally days 1-4; prednisone 60 mg/m² orally days 1-4 1

• Melphalan/prednisone/thalidomide (MPT) 1

  • Melphalan 0.25 mg/kg orally days 1-4; prednisone 2 mg/kg orally days 1-4; thalidomide 100-200 mg orally days 1-28 1

Relapsed/Refractory Disease Regimens

For relapsed disease, triplet therapy is preferred over doublet therapy, with regimens containing two novel agents plus steroids. 1, 2

Preferred regimens include:

• Carfilzomib/lenalidomide/dexamethasone (KRd) - Category 1 1, 5

  • Carfilzomib 20 mg/m² (cycle 1) escalating to 27 mg/m² IV days 1,2,8,9,15,16; lenalidomide 25 mg orally days 1-21; dexamethasone 40 mg days 1,8,15,22 1, 5

• Daratumumab/bortezomib/dexamethasone - Category 1 1

• Daratumumab/lenalidomide/dexamethasone - Category 1 1

• Bortezomib/dexamethasone - Category 1 for relapsed disease 1, 6

  • Bortezomib 1.3 mg/m² IV twice weekly for 2 weeks (days 1,4,8,11) followed by 10-day rest 6

• Pomalidomide/bortezomib/dexamethasone 1

• Cyclophosphamide/lenalidomide/dexamethasone (CRd) 1, 7

Key Drug Classes

Proteasome Inhibitors

• Bortezomib - First-generation, administered subcutaneously or IV 1, 6
• Carfilzomib - Second-generation, IV administration only 5
• Ixazomib - Oral proteasome inhibitor 1

Immunomodulatory Drugs (IMiDs)

• Lenalidomide - Most commonly used, oral administration 1, 8
• Thalidomide - Older agent with more side effects 1, 8
• Pomalidomide - Used in heavily pretreated patients 1

Alkylating Agents

• Cyclophosphamide - Used in combination regimens 1
• Melphalan - Standard for transplant conditioning and elderly patients 1

Corticosteroids

• Dexamethasone - Backbone of virtually all regimens 1

Critical Prescribing Considerations

Avoid myelotoxic agents (alkylating agents, nitrosoureas) in transplant candidates to preserve stem cell reserve. 1

Herpes zoster prophylaxis is mandatory for all patients receiving proteasome inhibitors. 1

Subcutaneous bortezomib is preferred over IV administration for patients with pre-existing or high-risk peripheral neuropathy. 1

Prophylactic anticoagulation (full-dose aspirin or therapeutic anticoagulation for high-risk patients) is required with immunomodulator-based therapy. 1

Consider harvesting peripheral blood stem cells prior to prolonged lenalidomide exposure in potential transplant candidates. 1

Common Pitfalls

Do not use single-agent chemotherapy - Multiple myeloma requires combination therapy with at least two, preferably three drugs from different classes. 1, 2

Do not delay treatment initiation - When CRAB criteria are present (hypercalcemia, renal insufficiency, anemia, bone lesions), immediate treatment is required. 2, 9

Do not overlook the increased risk of secondary cancers with lenalidomide maintenance therapy - This risk must be discussed with patients, though the survival benefits typically outweigh this concern. 1

Elderly or frail patients may require doublet rather than triplet regimens to manage toxicity, though triplet therapy remains the standard when tolerable. 1