CAR T-cell therapy for multiple myeloma (MM)

For decades, surgery, radiation, and chemotherapy were known as the three pillars of cancer treatment. In more recent decades, several new pillars have been added, as medical research has led to the development of new methods for treating cancer.

One of these pillars is immunotherapy, cancer treatments that work by aiding the body’s immune system in identifying and destroying cancer cells.

Immunotherapy has become an important treatment option for many types of cancer, and it is sometimes used in the treatment of multiple myeloma (MM), a type of cancer that affects white blood cells called plasma cells. This includes a type of immunotherapy called chimeric antigen receptor T cell (CAR T-cell) therapy, which involves collecting and modifying a person’s T cells (a type of white blood cell) to fight MM.

CAR T-cell therapy may be a treatment option for refractory or relapsed MM. Refractory MM is MM that has not responded to treatment. Relapsed refers to MM that has returned after successful treatment. Nearly every case of MM will relapse or become resistant to treatment at some point, and it will require different approaches to treatment.

An overview of MM

Like other cancers, MM results from the out-of-control growth of abnormal cells. In this case, plasma cells. Found in the bone marrow, plasma cells produce antibodies that help the body’s immune system fight infections. They are a type of B-cell.

When a person has MM, plasma cells have undergone mutations and become cancerous. Cancerous MM cells multiply at a much faster rate than normal plasma cells. This can crowd out healthy blood cells, weaken bones, and form tumors within bones. MM cells also produce abnormal antibodies, which can thicken the blood and buildup in organs (such as the kidneys).

Treatment for MM is individualized, meaning it will vary from person to person. There are many factors that will be considered when making treatment decisions. Because MM affects bone marrow and blood cells, and MM is often spread throughout the body, most treatment plans will include one or several drug therapies. Surgery and radiation therapy, and stem cell transplants, are also used in some cases.

MM is not curable, and the goals of treatment are reducing symptoms, slowing progression, putting the cancer into remission, and helping a person live as long as possible with the best quality of life possible.

CAR T-cell therapy for MM

As mentioned above, CAR T-cell therapy is a type of immunotherapy, and a potential treatment option for refractory or relapsed MM. To understand how CAR T-cell therapy works, it helps to take a closer look at a few key terms:

• T-cells. T cells or T lymphocytes are a type of white blood cell made in the bone marrow. There are several types. Some T cells are cytotoxic, meaning they will destroy cells they attach to, such as cancerous cells and cells that have become infected by viruses.
• Receptor. Receptors are proteins that are a part of a cell’s structure. Receptors work by attaching to other substances, such as hormones or proteins. Specific types of receptors can only bind to specific substances.
• Chimeric antigen receptors (or CARs) are laboratory-made receptors that bind with specific proteins found on cancer cells.

When a person is treated with CAR T-cell therapy:

• White blood cells will be collected from the person being treated using a procedure called leukapheresis, which uses special intravenous lines to filter out white blood cells and return the rest of the blood to the body. This procedure can take several hours and requires a person to remain seated or lying down.
• The collected sample will be sent to a lab, where a gene for a chimeric antigen receptor (CAR) will be added to the collected T cells. This will create T cells that are better equipped to attach to cancerous cells. Hundreds of millions of these CAR T cells will be produced in the lab.
• The CAR T cells will be administered to the person being treated through a single intravenous infusion. Sometimes a person will require chemotherapy in the days leading up to this infusion.

Different CAR T cell-therapies work on different type of cancer cells. There are two CAR T-cell therapies approved for MM, and others are under development. Others may be available in clinical trials.

Possible side effects of CAR T-cell therapy

Like other cancer treatments, CAR T-cell therapy can cause side effects. Potential side effects include:

• Weakened immune system
• Low blood cell counts
• Allergic reactions
• Abnormal levels of potassium, sodium, and other minerals.
• An increased risk of other types of blood cancers
• Cytokine release syndrome (CRS), a potentially life-threatening release of large amounts of inflammatory chemicals by the immune system that can cause fever, rapid heartbeat, low blood pressure, difficulty breathing, and organ failure.
• Immune effector cell-associated neurotoxicity syndrome (ICANS), problems with the nervous system that can lead to pain, problems with movement, seizures, and problems with cognition.

Side effects and the risk of side effects should always be discussed with a healthcare team before starting any cancer treatment. As with any type of cancer, your healthcare team will be your best source of information about your treatment options, and the many factors that will need to be considered when making treatment decisions, including a person’s age, overall health, the stage of MM, previous treatments received, and the specific genetic characteristics of their cancer.