Chimeric antigen receptor (CAR)-T cell therapy is a new multiple myeloma treatment option. It is a type of immunotherapy that can improve outcomes for people with advanced myeloma. Although CAR-T cell therapy can cause potentially serious side effects, it may also reduce or eliminate signs and symptoms of myeloma, even when other treatments have failed.

How Does CAR-T Cell Therapy Work?

CAR-T cell therapy helps the body’s immune system fight cancer more effectively. There are a few steps in the CAR-T cell therapy process:

• T cells (a type of immune cell) are collected from a person with myeloma.
• T cells are genetically changed in the laboratory.
• T cells are returned to the body.
• Modified T cells recognize and kill cancer cells.

Collecting T Cells

T cells are a type of white blood cell. They work as a part of the immune system, killing infected cells and coordinating other immune cells. CAR-T cell therapy enables T cells to also attack cancer cells.

The first step of CAR-T cell therapy is collecting a person’s T cells. To collect T cells, doctors use a process called apheresis in which a machine removes blood from the body and separates the T cells. The rest of the blood and other blood cells are then put back in the body. This process leaves doctors with a sample of T cells, which is sent to a laboratory.

Genetically Engineering T Cells

In the laboratory, the T cells are genetically engineered (changed). Doctors use a virus to put new DNA into the T cells. This virus is inactive, meaning it can’t cause infections.

The new DNA acts as a set of instructions that tells T cells how to create CARs. A CAR is a protein that sits on the outer surface of the modified T cell. CARs can attach to specific proteins found on cancer cells. Genetically engineered T cells that have CARs, called CAR-T cells, can now find and attack cancer cells.

The changed T cells are grown in the lab. Each CAR-T cell makes many copies of itself, leading to a large number of new T cells. These cells are frozen until they are ready to be used. This entire process may take up to three weeks.

Returning T Cells to the Body

Once the CAR-T cells are ready, the person with myeloma returns to the hospital or treatment center. The new T cells are returned to the body through an intravenous (IV) infusion.

A person receiving CAR-T cell therapy often first undergoes lymphodepletion (a round of chemotherapy treatments) before receiving their new T cells. Lymphodepletion removes old T cells, making room for the new ones, and helps the CAR-T cells better fight cancer cells.

Killing Cancer Cells

Within the body, CAR-T cells continue to grow and multiply and begin killing cancer cells. CAR-T cells can remain in the body for many months and may help prevent cancer from returning.

After receiving a CAR-T cell infusion, people often have to stay in the hospital for several weeks. This allows doctors to determine whether the treatment is working and manage any side effects. Even after being discharged from the hospital, people may need to stay close to the treatment center for a month or more in case any complications occur.

CAR-T Cell Therapy in Multiple Myeloma

CAR-T cell treatments are available for several forms of blood cancer, including multiple myeloma and different types of leukemia and lymphoma. The U.S. Food and Drug Administration (FDA) approved a specific type of CAR-T cell therapy for multiple myeloma in March 2021. In this treatment, CAR-T cells are engineered to recognize a protein called B-cell maturation antigen (BCMA). Cancerous plasma cells often have BCMA on their outer surface, making it easy for CAR-T cells to find and kill them. This approved CAR-T cell treatment is called Abecma (idecabtagene vicleucel) or ide-cel.

Who Is Eligible for CAR-T Cell Therapy?

People with myeloma need to meet certain conditions before they are eligible for CAR-T cell therapy. Their myeloma needs to be refractory (resistant to treatment) or relapsed (came back after being treated). Additionally, they need to have already tried at least four other treatments, including one or more treatments from each of the following categories:

• Immunomodulatory drugs, such as Revlimid (lenalidomide) or Pomalyst (pomalidomide)
• Proteasome inhibitors, like Velcade (bortezomib), Kyprolis (carfilzomib), or Ninlaro (ixazomib)
• Anti-CD38 monoclonal antibodies, like Darzalex (daratumumab) or Sarclisa (isatuximab-irfc)

How Well Does CAR-T Cell Therapy Work?

CAR-T cell therapy is not a cure for multiple myeloma. However, it may help people with myeloma live longer or keep their cancer cells under control.

There have been two main studies looking at ide-cel. The first study found that most people who received this treatment had reduced cancer signs and symptoms. In a second larger study called KarMMa, researchers found that CAR-T cell therapy had many beneficial effects for myeloma:

• 3 out of 4 people had fewer signs of cancer.
• 1 out of 3 people had a complete response (all signs of cancer were gone).
• Among people who had a complete response, 2 out of 3 were in remission (had no signs of cancer) for at least one year.

This approved CAR-T cell therapy does not work for everyone with multiple myeloma, and cancer sometimes comes back after this treatment is done. However, it has worked very well for many people with hard-to-treat myeloma, even when other treatments have failed. It’s too soon to say how well this treatment works in the long term.

The Future of CAR-T Cell Therapy in Myeloma

Other CAR-T cell treatments are also currently being studied in clinical trials. Current studies and clinical trials are focused on targeting BCMA, a TNF receptor superfamily. These other treatments may work even better than ide-cel. Researchers are also looking at the effects of combining CAR-T cell therapy with other medications. Eventually, additional CAR-T cell treatments may be approved to treat multiple myeloma.

The Risks of CAR-T Cell Therapy

In the ide-cel clinical trials, CAR-T cell therapy caused side effects for nearly every participant. For this reason, the treatment is only available at certain certified locations where health care providers are specially trained to recognize and treat any problems. Researchers are continuing to study the safety of CAR-T cell therapy and may release additional information about this treatment in the future.

Fortunately, most side effects from this treatment are mild. CAR-T cell therapy generally causes fewer side effects than a stem cell transplant does. Before undergoing CAR-T cell therapy, people with myeloma should thoroughly discuss the risks and benefits with their doctor. Treatments are available to help with many of CAR-T cell therapy’s side effects.

Cytokine Release Syndrome

Cytokine release syndrome (CRS) is a condition that sometimes develops following CAR-T cell therapy. When T cells are activated, they make a lot of cytokines (chemicals that act as messengers among cells of the immune system and can lead to inflammation). CRS occurs when high levels of cytokines begin to damage other tissues in the body. CRS can lead to organ failure and is sometimes life-threatening. CRS may cause flu-like symptoms, including fever, chills, breathing problems, and confusion.

In the larger ide-cel trial, 84 percent of participants had CRS. In most cases, this condition was mild. Only 1.5 percent of people had severe CRS. Severe CRS following CAR-T cell therapy can be treated with Actemra (tocilizumab) or corticosteroid medications.

Neurotoxicity

CAR-T cell therapy can cause neurotoxicity (damage to the brain or nerves). Symptoms of neurotoxicity may include confusion, trouble speaking or listening, and stupor (a lack of response to the outside world).

Other Side Effects

CAR-T cell therapy can lead to some other common side effects, such as:

• Tiredness
• Infections
• Muscle aches
• Diarrhea
• Nausea
• Swelling
• Fever
• Cough
• Headache
• Loss of appetite

If you choose to try CAR-T cell therapy, talk to your doctor about possible side effects. Ask your health care team which side effects may be a sign of a more serious health problem.

Talk With Others Who Understand

MyMyelomaTeam is the social network for more than 11,000 people with multiple myeloma and their loved ones. On MyMyelomaTeam, members come together to ask questions, give advice, and share their stories with others who understand life with multiple myeloma.

Are you living with multiple myeloma? Share your experiences in the comments below, or start a conversation by posting on MyMyelomaTeam.