The treatment of multiple myeloma is highly individualized. The approach chosen will depend on a variety of factors, including the stage of cancer, the patient’s overall health, and his or her symptoms. Options include:
Triplet or Quadruplet Drug Combination Therapy
First-line treatment (induction therapy) for newly diagnosed multiple myeloma typically involves a three-drug (triplet) or four-drug (quadruplet) combination. These drug regimens help reduce the tumor burden, reverse organ damage, and achieve the best outcomes possible. They also help to prepare eligible patients for an autologous stem cell transplant (ASCT). The drugs used for MM treatment include:
Proteasome Inhibitors
Proteasome inhibitors (PIs) target the overproduction of M proteins. There are three main PIs used in multiple myeloma treatment:
- Bortezomib, which is given via injection
- Carfilzomib, which is given intravenously
- Ixazomib, which is an oral pill taken at home
Common side effects of PIs include gastrointestinal upset, such as nausea and diarrhea; fatigue; lowered blood platelet counts; and potential neuropathy.
Immunomodulatory Drugs (IMiDs)
Immunomodulatory drugs (IMiDs) are pill-based therapies used to treat multiple myeloma. They target and attack tumor cells while also boosting the patient’s immune system to fight the cancer. IMiDs are also helpful for protecting bones from the weakening that MM can cause. They block the cells that break down bones and increase the cells that build new bone.
There are three main types of IMiDs used for MM:
- Lenalidomide
- Pomalidomide
- Thalidomide
Although IMiDs are very effective, patients need to be monitored for the side effects they can cause, including blood clots, low blood counts, and birth defects in pregnant women.
Monoclonal Antibodies
Monoclonal antibodies are lab-made proteins that imitate natural immune system defenses. To treat multiple myeloma, they target specific proteins on the surface of cancer cells to destroy them. They can either flag the cells so the immune system will attack the cancer, directly kill the cancer cells themselves, or boost the immune system to detect the cancer cells and strengthen infection-fighting cells. There are three main types of monoclonal antibodies used in MM treatment:
- Daratumumab
- Elotuzumab
- Isatuximab
Side effects of these drugs include infusion reactions, such as fever or chills, low blood cell counts, fatigue, and infections.
Autologous Stem Cell Transplant (ASCT)
After patients complete induction therapy, they may be eligible for an autologous stem cell transplant (ASCT). This process involves removing the patient’s healthy stem cells, administering a high dose of chemotherapy to destroy cancer cells, and reinfusing the patient’s healthy stem cells.
After the transplant, patients typically need maintenance therapy to control any remaining myeloma cells and extend remission. Although ASCT is not a cure for multiple myeloma, it is an effective tool for achieving deep remissions and prolonging progression-free survival.
CAR-T Cell Therapy
If patients are experiencing relapsing or refractory multiple myeloma, CAR-T cell therapy may be used. It involves extracting T-cells – key components of the immune system — from the patient’s body, genetically modifying them to target the BCMA protein on myeloma cells, and reinfusing them into the patient’s body. Once they’re infused, these cells work to hunt down and attack cancer cells. There are two primary options for CAR-T cell therapy at this time:
- Ciltacabtagene autoleucel, which is for patients who have had at least one prior line of therapy
- Idecabtagene vicleucel, which is for those with at least two prior lines of therapy
CAR-T cell therapy causes a powerful immune response, so patients must be closely monitored for side effects, including cytokine release syndrome (CRS), neurologic toxicities, and cytopenias (low blood counts).
Bispecific Antibodies
Bispecific antibodies are among the newest multiple myeloma therapies. They are a type of immunotherapy that attaches to two different targets, bringing them together. The first target is the protein BCMA or GPRC5D on the surface of myeloma cells. The second is theCD3 receptor on the patient’s T-cells. By bringing the cancer cell and the immune cell together, the T-cell is activated to destroy the tumor. These therapies are mostly used for patients with relapsed, refractory, or heavily pre-treated MM. They include:
- Teclistamab, which targets BCMA
- Talquetamab, which targets GPRC5D
The risks of bispecific antibodies include cytokine release syndrome (CRS), neurologic toxicities, and infections.
Drug Class Chart
Drug Class | Example Drugs | Method of Administration | Key Side Effects |
Proteasome Inhibitors | - Bortezomib (Velcade)
- Carfilzomib (Kyprolis)
- Ixazomib (Ninlaro)
| Subcutaneous Injection, intravenous (IV) infusion, or oral pill | - Gastrointestinal upset (nausea, diarrhea)
- Fatigue
- Lowered blood platelet count
- Potential neuropathy
|
Immunomodulatory Drugs (IMiDs) | - Lenalidomide (Revlimid)
- Pomalidomide (Pomalyst)
- Thalidomide
| Oral pill | - Blood clots
- Low blood counts
- Birth defects in pregnant women
|
Monoclonal Antibodies | - Daratumumab (Darzalex)
- Elotuzumab (Empliciti)
- Isatuximab (Sarclisa)
| Intravenous infusion or subcutaneous injection | - Infusion reactions (fever or chills)
- Low blood cell counts
- Fatigue
- Infections
|
CAR-T Cell Therapy | - Ciltacabtagene autoleucel (Carvykti)
- decabtagene vicleucel (Abecma)
| IV infusion | - Cytokine Release Syndrome (CRS)
- Neurologic toxicities
- Cytopenias (low blood counts)
|
Bispecific Antibodies | - Teclistamab (Tecvayli)
- Talquetamab (Talvey)
| Intravenous infusion or subcutaneous injection | - Cytokine Release Syndrome (CRS)
- Neurologic toxicities
- Infections
|