Medication Summary
Multiple myeloma (MM) is treated with several categories of medications. Chemotherapeutic agents, corticosteroids, and monoclonal antibodies are used to reduce the disease burden, and bisphosphonates are used to promote bone healing and to provide secondary prophylaxis against skeletal-related events (eg, hypercalcemia, bone fracture, spinal cord compression, need for radiation, and need for surgery). In addition, erythropoietin is used to treat anemia, either alone or in conjunction with chemotherapy.
Chemotherapeutic Agents
Class Summary
The choice of chemotherapy depends on several factors, including the patient’s performance status, age, renal function, desire for inpatient or outpatient therapy, and likelihood of receiving future autologous stem cell transplantation.
In patients with renal failure or highly aggressive disease, therapy with vincristine, Adriamycin (doxorubicin), and dexamethasone (VAD) may be preferred. In elderly patients or patients in whom autologous transplantation is not possible in the future, melphalan and prednisone (MP) therapy is preferred because of its ease of administration and low toxicity.
Cyclophosphamide (Cytoxan, Neosar)
Cyclophosphamide is chemically related to nitrogen mustards. It is an alkylating agent, and its mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Melphalan (Alkeran)
The most widely used regimen is MP. Melphalan is an alkylating agent and a derivative of mechlorethamine that inhibits mitosis by cross-linking DNA strands. It is indicated for the palliative treatment of multiple myeloma.
Doxorubicin (Adriamycin, Rubex)
Doxorubicin is part of VAD therapy. It inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA; these 2 events, in turn, can inhibit growth of neoplastic cells.
Doxorubicin liposomal (Doxil)
Doxorubicin liposomal is a pegylated formulation that protects the liposomes and, thereby, increases blood circulation time. The drug inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA; these 2 events can, in turn, inhibit growth of neoplastic cells.
Vincristine (Oncovin)
Vincristine inhibits cellular mitosis by inhibition of intracellular tubulin function, binding to microtubules, and synthesis of spindle proteins in the S phase. Vincristine is part of VAD therapy. Its mechanism of action is complex and includes depolymerization of microtubules.
Bortezomib (Velcade)
Bortezomib is the first drug approved in the group of anticancer agents known as proteasome inhibitors. The proteasome pathway is an enzyme complex existing in all cells, which degrades ubiquitinated proteins that control the cell cycle and cellular processes and maintains cellular homeostasis. Reversible proteasome inhibition disrupts pathways supporting cell growth, thus decreasing cancer cell survival. Bortezomib is indicated for patients with multiple myeloma. Development of peripheral neuropathy is a limiting factor. A decreased incidence of peripheral neuropathy has been observed with SC administration compared with the IV route.
Carfilzomib (Kyprolis)
Proteasome inhibitor; elicits antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells. It is indicated as monotherapy, in combination with dexamethasone, or in combination with lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma in patients who have received at least 1 prior line of therapy.
Ixazomib (Ninlaro)
Reversible proteasome inhibitor. It preferentially binds and inhibits the chymotrypsinlike activity of the beta 5 subunit of the 20S proteasome. It is indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy.
Panobinostat (Farydak)
Panobinostat is a histone deacetylase (HDAc) inhibitor. HDAc catalyzes the removal of acetyl groups from the lysine residues of histones and some nonhistone proteins. Inhibition of HDAc activity results in increased acetylation of histone proteins and an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. It is indicated in combination with bortezomib and dexamethasone for treatment of multiple myeloma in patients who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Meticorten)
The most widely used regimen is MP. Prednisone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
Dexamethasone (Decadron)
Dexamethasone is part of many treatment regimens for multiple myeloma. Dexamethasone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.
Monoclonal Antibodies
Class Summary
Monoclonal antibodies that target proteins expressed on multiple myeloma cells (eg, CD38, SLAMF7) have been approved.
Denosumab (Xgeva)
Monoclonal antibody that specifically targets RANKL. It binds to RANKL and inhibits its binding to RANK receptor, thereby preventing osteoclast formation. This results in decreased bone resorption and increases bone mass in osteoporosis. RANKL inhibition decreases tumor-induced bone destruction and SREs. Denosumab is indicated for prevention of SREs in patients with multiple myeloma.
Daratumumab (Darzalex)
Monoclonal antibody that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is indicated for patients with multiple myeloma who have received at least 3 prior treatments, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are double-refractory to a PI and IMiD. Other regimens for relapsed/refractory MM are approved for daratumumab in combination with dexamethasone plus bortezomib or lenalidomide or pomalidomide. It is also indicated for newly diagnosed MM in patients ineligible for ASCT as part of various combination regimens. May also be considered in newly diagnosed MM in patients who are eligible for ASCT in combination with bortezomib, thalidomide, and dexamethasone.
Elotuzumab (Empliciti)
Humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (signaling lymphocytic activation molecule family member 7) protein. SLAMF7 is expressed on myeloma cells and natural killer cells and plasma cells. Facilitates the interaction with natural killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity. It is indicated in combination with lenalidomide and dexamethasone for multiple myeloma in patients who have received 1-3 prior therapies. Elotuzumab is also indicated in combination with pomalidomide and dexamethasone for patients with multiple myeloma who have received 2 or more prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab (Sarclisa, isatuximab-irfc)
Anti-CD38 monoclonal antibody indicated for relapsed or resistant multiple myeloma in combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor, and in combination with carfilzomib and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
Elranatamab (Elrexfio)
Elranatamab is a humanized BCMA-CD3 bispecific antibody. FDA granted accelerated approval for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Talquetamab (Talquetamab-tgvs, Talvey)
Talquetamab is a potential first-in-class, investigational T-cell redirecting bispecific antibody targeting both GPRC5D, a novel multiple myeloma target that does not shed over time, and CD3, a component of the T-cell receptor. It was granted accelerated approval to talquetamab (Talvey) for relapsed or refractory multiple myeloma in adults who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Interferons
Class Summary
Interferons are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alfa-, beta-, and gamma-interferons may be administered topically, systemically, and intralesionally.
Interferon alfa-2B (Intron A)
Interferon alfa-2B is a protein product manufactured by recombinant DNA technology. The mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.
Immunosuppressant Agents
Class Summary
Immunosuppressant agents inhibit key factors in the immune system that are responsible for immune reactions.
Thalidomide (Thalomid)
Thalidomide, when used in combination with dexamethasone, is indicated for the treatment of patients with newly diagnosed multiple myeloma. Thalidomide is an immunomodulatory agent that may suppress excessive production of tumor necrosis factor (TNF)-alpha and may down-regulate selected cell-surface adhesion molecules involved in leukocyte migration. Because of concerns regarding teratogenicity, thalidomide can only be prescribed by registered physicians and is dispensed by registered pharmacists. Patients must participate in ongoing surveys to receive therapy, and only a 28-d supply can be prescribed at a time.
Lenalidomide (Revlimid)
Lenalidomide is indicated in combination with dexamethasone for multiple myeloma. It is structurally similar to thalidomide. Lenalidomide elicits immunomodulatory and antiangiogenic properties. It inhibits proinflammatory cytokine secretion and increases anti-inflammatory cytokines from peripheral blood mononuclear cells.
Pomalidomide (Pomalyst)
Thalidomide analogue indicated in combination with dexamethasone for patients with multiple myeloma who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. Also used in combination with elotuzumab and dexamethasone.
Anti-BCMA Antibodies
Class Summary
Agents in this drug class are antibody-drug conjugates. The antibody component is an afucosylated IgG1 directed against B-cell maturation agent (BCMA), a protein expressed on normal B lymphocytes and multiple myeloma cells. The small molecule component is MMAF, a microtubule inhibitor.
Belantamab mafodotin (Belantamab mafodotin-blmf, Blenrep)
Upon binding to BCMA, belantamab mafodotin-blmf is internalized followed by release of MMAF via proteolytic cleavage. The released MMAF intracellularly disrupts the microtubule network, leading to cell cycle arrest and apoptosis. It also has antitumor activity in multiple myeloma cells and mediated killing of tumor cells through MMAF-induced apoptosis, as well as by tumor cell lysis through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). It is indicated for relapsed or refractory MM in patients who were previously treated with 4 or more prior therapies.
Teclistamab (Tecvayli)
Teclistamab is a bispecific T-cell engaging antibody binds to CD3 receptor surface of T-cells and B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In October 2022, the FDA granted accelerated approval for adults with relapsed or refractory MM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
CAR T-Cell Therapies
Idecabtagene vicleucel (Abecma)
B-cell maturation antigen (BCMA)-directed genetically modified autologous CAR T-cell therapy is indicated for relapsed or refractory MM after ≥4 prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Each idecabtagene vicleucel dose is customized using a patient’s own T-cells to help fight the myeloma. These T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing myeloma cells. Once modified, the cells are infused back into the patient.
Ciltacabtagene autoleucel (Carvykti)
CAR-T cell therapy featuring 2 BCMA-targeting single domain antibodies is indicated for relapsed or refractory MM in adults who were previously treated with ≥4 prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.
Selective Inhibitor of Nuclear Export
Class Summary
A selective inhibitor of nuclear export (SINE) acts on tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). Inhibition of XPO1 leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins (eg, c‐myc, cyclin D1), cell cycle arrest, and apoptosis of cancer cells.
Selinexor (Xpovio)
Indicated in combination with dexamethasone for adults with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.
Bisphosphonates
Class Summary
Bisphosphonates inhibit bone resorption via action on osteoclasts or osteoclast precursors.
Pamidronate (Aredia)
Pamidronate inhibits normal and abnormal bone resorption. It appears to inhibit bone resorption without inhibiting bone formation and mineralization. The optimal timing and duration of therapy are being studied. Pamidronate is administered intravenously (IV) over 2 hours. Newer drugs similar in structure and function are being studied and may have improved efficacy and greater convenience.
Zoledronic acid (Zometa)
Zoledronic acid inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors. It is effective in treating the hypercalcemia of malignancy.
Colony-stimulating Factors
Class Summary
Colony-stimulating factors induce erythropoiesis.
Epoetin alfa, erythropoietin (Epogen, Procrit)
Erythropoietin stimulates the division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from bone marrow into the blood stream.
Erythropoietin is a naturally occurring hormone produced by the kidneys to stimulate bone marrow production of red blood cells. In patients with MM, administration of exogenous erythropoietin may correct anemia, leading to a significant improvement in performance status and quality of life.
CXCR4 Inhibitors
Class Summary
These drugs inhibit the C-X-C motif chemokine receptor 4 (CXCR4) and block binding of its cognate ligand, stromal-derived factor-1α (SDF-1α)/CXCL12. SDF-1α and CXCR4 play a role in trafficking and homing of hematopoietic stem cells to the marrow compartment.
Motixafortide (Aphexda)
Indicated in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma.
Plerixafor (Mozobil)
Indicated in combination with filgrastim to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with multiple myeloma and non-Hodgkin lymphoma.
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Amyloidosis infiltrating the tongue in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Radiograph of the skull demonstrating a typical lytic lesion in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Bone marrow aspirate demonstrating plasma cells of multiple myeloma. Note the blue cytoplasm, eccentric nucleus, and perinuclear pale zone (or halo). All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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Bone marrow biopsy demonstrating sheets of malignant plasma cells in multiple myeloma. All images and text are (c) 2002 by the American Society of Hematology. All rights reserved.
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- Overview
- Presentation
- DDx
- Workup
- Approach Considerations
- Blood Studies
- Urine Collection
- Electrophoresis and Immunofixation
- Quantitative Immunoglobulin Levels (IgG, IgA, IgM)
- Beta-2 Microglobulin and C-Reactive Protein
- Serum Viscosity
- Radiography
- Magnetic Resonance Imaging
- Positron Emission Tomography
- Bone Scan
- Aspiration and Biopsy
- Histologic Findings
- Cytogenetic Analysis
- Staging
- Show All
- Treatment
- Approach Considerations
- Chemotherapy and Immunotherapy
- Transplantation
- Chimeric antigen receptor (CAR) T-Cell Therapy
- Interferon Alfa Therapy
- Radiation Therapy
- Therapy for Skeletal-Related Events
- Adjunctive Therapy for Complications
- Surgical Care
- Dietary Measures
- Physical Activity
- Prevention of Multiple Myeloma
- Consultations
- Long-Term Monitoring
- Show All
- Guidelines
- Medication
- Questions & Answers
- Media Gallery
- References
