Medications for Multiple Myeloma (Cancer)
Multiple myeloma is a cancer of plasma cells in the bone marrow, and the medications used to treat it include proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (lenalidomide, pomalidomide, thalidomide), monoclonal antibodies (daratumumab, elotuzumab, isatuximab), histone deacetylase inhibitors (panobinostat), alkylating agents (melphalan, cyclophosphamide), and corticosteroids (dexamethasone, prednisone). 1
Proteasome Inhibitors (PIs)
These drugs block the proteasome system that cancer cells use to break down proteins, leading to cancer cell death:
- Bortezomib: First-generation PI, administered intravenously or subcutaneously (subcutaneous preferred to reduce peripheral neuropathy risk) 1, 2
- Carfilzomib: Second-generation PI with superior efficacy compared to bortezomib in relapsed disease, showing improved progression-free survival and overall survival 1
- Ixazomib: Oral second-generation PI, offering convenience for patients 1
- Marizomib, oprozomib, delanzomib: Newer-generation PIs under investigation 3, 4
Immunomodulatory Drugs (IMiDs)
These agents modulate the immune system and have direct anti-myeloma effects:
- Lenalidomide: Most commonly used IMiD, standard for both induction and maintenance therapy 1, 2, 5
- Pomalidomide: Third-generation IMiD used primarily in lenalidomide-refractory disease 1
- Thalidomide: First-generation IMiD, less commonly used now due to toxicity profile 1, 6
Important caveat: All IMiDs require thromboprophylaxis, herpes zoster prophylaxis, and are teratogenic with strict pregnancy prevention requirements through REMS programs 2, 7
Monoclonal Antibodies (MoAbs)
These target specific proteins on myeloma cells:
- Daratumumab: Anti-CD38 antibody, now considered preferred first-line therapy when combined with lenalidomide and dexamethasone for transplant-ineligible patients 1, 2, 7
- Elotuzumab: Anti-SLAMF7 antibody used in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone 1, 8
- Isatuximab: Anti-CD38 antibody showing efficacy in combination with carfilzomib and dexamethasone 1, 4
Bispecific Antibodies and CAR-T Therapies
Novel immunotherapies for heavily pretreated disease:
- Teclistamab, elranatamab, talquetamab: BCMA-targeting or GPRC5D-targeting bispecific T-cell engagers for relapsed/refractory disease after ≥4 prior therapies 8
- BCMA-directed CAR-T cells: Approved for triple-class refractory multiple myeloma 1
Histone Deacetylase Inhibitors (HDACi)
- Panobinostat: Used in combination with bortezomib and dexamethasone, particularly beneficial in high-risk cytogenetics and bortezomib-refractory disease 1
Alkylating Agents
- Melphalan: High-dose melphalan (200 mg/m²) is standard conditioning for autologous stem cell transplantation 2
- Cyclophosphamide: Used in various combination regimens, particularly with pomalidomide 1
Corticosteroids
- Dexamethasone: Backbone of most myeloma regimens, dose-reduced to 20 mg weekly for patients >75 years and 8-20 mg weekly for frail patients 2
- Prednisone: Used in specific combinations like bortezomib-melphalan-prednisone 9
Antibody-Drug Conjugates
- Belantamab mafodotin: BCMA-targeting antibody delivering monomethyl auristatin F to myeloma cells 8
Other Agents
- Selinexor: XPO-1 inhibitor approved for relapsed/refractory disease 4
- Bisphosphonates: Not anti-cancer agents but essential supportive care to reduce skeletal-related events 2, 9
Critical distinction: Bisphosphonates (like zoledronic acid) manage bone disease complications but do not treat the cancer itself—they are supportive care medications 2, 9