Drug therapies for multiple myeloma
The main types of drug therapies used to treat multiple myeloma are proteasome inhibitors, immunomodulatory drugs (IMiDs), steroids, histone deacetylase (HDAC) inhibitors, antibodies, and chemotherapy. Each works in a different way, but with the common goal of controlling and destroying multiple myeloma cells.
In addition to the many drugs currently approved to treat multiple myeloma, there are clinical trials under way to evaluate the benefits and risks of drugs that are in development.
Proteasome inhibitors are a staple of multiple myeloma treatment and are used throughout all stages of disease. The three discussed below are approved for treatment of multiple myeloma:
Proteasomes are protein complexes that help cells—including cancer cells—dispose of old proteins so they can be replaced by newer versions. Proteasome inhibitors are drugs that prevent cancer cells from doing this. As the old proteins pile up, the cancer cells die.
An intravenous (IV) drug that is given to patients as a first-line treatment, as well as to patients with relapsed disease. Velcade is often given in combination with other drugs and can be given to patients who have previously received Velcade.
An IV drug (either in combination or alone) given to patients who have previously received at least one other treatment for multiple myeloma.
An oral drug (used in combination with another drug) that is given to patients who have previously received another treatment for multiple myeloma.
This class of immunotherapy drugs is the mainstay of standard regimens used to treat multiple myeloma. IMiDs work by regulating certain aspects of the immune system. They can activate certain immune cells, prevent certain types of growth signals for cancer cells, and directly kill myeloma cells. IMiDs used to treat multiple myeloma include:
An oral drug used throughout all stages of multiple myeloma, in combination with dexamethasone. Other combinations using Revlimid are being studied.
An oral drug used in patients with relapsed/refractory multiple myeloma, high-risk multiple myeloma, or those with kidney problems. It is more potent than Revlimid or Thalomid.
An oral drug used in combination with other drug(s) throughout all stages of multiple myeloma.
Steroids are a staple of multiple myeloma treatment and are used at all stages of the disease. In high doses, steroids can kill multiple myeloma cells. They can also decrease inflammation by stopping white blood cells from flowing to the disease-affected areas, helping relieve pain and pressure. Additionally, steroids may be used to reduce nausea and vomiting caused by chemotherapy and other forms of treatment.
Two steroids that are commonly used in multiple myeloma are dexamethasone and prednisone. They may be used in combination with other multiple myeloma drugs.
Side effects of steroids include high blood sugar, weight gain, sleeping problems, and changes in mood. Over time, steroids may suppress the immune system and weaken bones. These side effects usually go away after patients stop taking these drugs.
Some multiple myeloma cells make too much of the histone deacetylase (HDAC) protein, allowing malignant cells to quickly grow and divide. HDAC inhibitors target this process, causing cancer cell death.
Farydak (panobinostat) is currently the only HDAC inhibitor approved to treat multiple myeloma. It is given in combination with Velcade and dexamethasone to patients who have received at least two other treatments for multiple myeloma.
Other HDAC inhibitors are being studied in clinical trials.
Monoclonal antibodies are a type of immunotherapy. These drugs enhance the cancer-fighting abilities of a patient’s own immune system by introducing antibodies into the body that target specific proteins found on multiple myeloma cells.
Four monoclonal antibodies have been approved for use against multiple myeloma: Empliciti (elotuzumab), Darzalex (daratumumab), Sarclisa (isatuximab), and Xgeva (Denosumab). Empliciti recognizes SLAMF7, a protein expressed on myeloma and natural killer (NK) cells. Empliciti dually stimulates NK cell activation and tags myeloma cells for recognition, leading to tagged myeloma cell death. Darzalex and Sarclisa recognize an antigen called CD38 that is made by myeloma cells and helps flag these cells for destruction and kills them directly. Xgeva, also known as Denosumab, is a monoclonal antibody that was approved by the FDA for prevention of skeletal-related events in patients with multiple myeloma. It is made by Amgen. Several new monoclonal antibodies are being studied by the Multiple Myeloma Research Foundation.
The MMRF is also studying the use of checkpoint inhibitors, another type of drug that is often made of antibodies, in multiple myeloma. Checkpoint inhibitors are already used in the treatment of many other cancers.
Novel Mechanisms of Action
Some of the newest drugs used to treat multiple myeloma do not fit the classification of any existing drugs. These new drugs have a novel mechanism of action, which means that they work in different ways than drugs in the other classes. Drugs with novel mechanisms of action target certain proteins involved in cell growth and division. These drugs may target proteins that are specific to myeloma cells or all cells.
This drug is a selective inhibitor of nuclear export (SINE) that binds to and interferes with the function of a nuclear export protein called XPO1. Interfering with this protein ultimately leads to myeloma cell death. XPOVIO is an oral drug (used in combination with dexamethasone) that is given to patients who have previously received at least four prior treatment regimens and are refractory to proteasome inhibitors, immunomodulatory drugs, and Darzalex.
Supportive Care Drugs
There are also drug therapies available to help relieve multiple myeloma symptoms, such as bone disease or kidney failure. Symptom management, through drugs and other interventions, is known as “supportive care.”
“Chemotherapy” can be a scary word for many cancer patients, as some may believe it will cause extreme suffering and keep them from their daily activities. The reality is that many people can continue working, spending time with family and friends, and living their lives while receiving chemotherapy.
Chemotherapy uses drugs to treat cancer by killing cells that are in the process of dividing. Because cancer cells grow and divide more frequently than most normal, healthy cells, they are affected more than normal cells. However, some healthy cells will be affected by chemotherapy as well. This is what causes side effects. Most side effects can be prevented or lessened in severity.
In the treatment of multiple myeloma, chemotherapy is most often used in preparation for a stem cell transplant.
Common chemotherapy drugs for multiple myeloma include:
- Doxil (liposomal doxorubicin)
- Evomela (melphalan)
- Cytoxan (cyclophosphamide)
- VP-16 (etoposide)
- Adriamycin (doxorubicin)
- Treanda (bendamustine)
- Oncovin (vincristine)
Some chemotherapy drugs are given orally, while others are given intravenously (through a vein). Often, several drugs are given together in combination because combining them has been shown to work better at stopping tumors, while causing fewer side effects.
Chemotherapy treatments are given in schedules called cycles, which typically last 3 or 4 weeks. Some drugs are taken daily, while others are given weekly or once per cycle. One course of treatment typically consists of 4 to 6 cycles, lasting a total of about 4 to 6 months.
Radiation therapy, which uses high-energy particles or rays to damage cancer cells and prevent them from growing, is proven to effectively treat multiple myeloma in specific situations and/or reduce complications from bone disease. Radiation therapy may also be called radiotherapy, X-ray therapy, or irradiation.
Radiation therapy is administered using a machine that directs high-energy rays at the patient’s body. The rays may be directed at a particular area of bone (called “local radiation”) or at a larger part of the body. When a patient receives radiation therapy of the entire body, it is called total body irradiation (TBI). TBI and radiation therapy directed at large parts of the body are rarely used in the treatment of multiple myeloma.
In high doses, local radiation therapy (sometimes given with chemotherapy) is used to treat solitary tumors in bone or soft tissue (plasmacytomas). In low doses, local radiation therapy is sometimes used to relieve uncontrolled pain or to help prevent or treat bone fractures or spinal-cord compression.
Along with cancer cells, some normal cells may be affected by radiation; fast-dividing cells, such as those in the bone marrow and the lining of the digestive tract, are most susceptible to damage by radiation therapy. However, most normal cells appear to recover fully from the effects of treatment.
Radiation therapy often makes patients feel tired and lose their appetite, and it can make the skin above the treated area more sensitive and irritated. Other side effects depend on the part of the body that was treated. For example, radiation to the pelvic area may cause suppression of the bone marrow and lead to reduced blood cell counts. This is because half of the body’s bone marrow is found in the pelvic bones. Radiation to the pelvic area can also affect the lower digestive tract, causing symptoms such as diarrhea, spasms and, in rare cases, bleeding. It can also affect the reproductive organs.