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Chimeric antigen receptor T-cell therapy (CAR T-cell therapy) is an advanced multiple myeloma treatment option. Specifically, CAR T-cell therapy 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.
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:
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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 leukapheresis, 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 returned to the body, leaving doctors with a sample of your T cells to send to the laboratory.
In the laboratory, the T cells are genetically engineered with new DNA.
The new DNA acts as a set of instructions that tells T cells how to create chimeric antigen receptors (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 multiplied in the lab. Each CAR T cell makes many copies of itself to form a large number of new T cells. These are frozen until they’re ready to be used. This process may take up to three weeks.
Once the CAR T cells are ready, the person returns to the hospital or treatment center. The new T cells are returned to the body through an intravenous (IV) infusion.
Before CAR T-cell infusion, people usually receive lymphodepleting chemotherapy. This treatment reduces certain immune cells and helps create conditions that allow the CAR T cells to expand and work more effectively.
Within the body, CAR T cells continue to grow and multiply and begin killing cancer cells.
CAR T cells can remain in the body after treatment and continue to recognize and attack myeloma cells.
After receiving a CAR T-cell infusion, people need close monitoring for side effects. Some people are hospitalized, while others may be monitored as outpatients. People are generally advised to stay close to a healthcare facility for at least two weeks after treatment.
There are currently two U.S. Food and Drug Administration (FDA)-approved CAR T-cell therapies for multiple myeloma. In both of these therapies, T cells are engineered to recognize a protein called B-cell maturation antigen (BCMA). Cancerous plasma cells often have BCMA on their outer surface, which allows CAR T cells to recognize and attack them.
The FDA approved the first CAR T-cell therapy for multiple myeloma, idecabtagene vicleucel (Abecma), in 2021. This drug is also referred to as ide-cel.
Ciltacabtagene autoleucel (Carvykti), or cilta-cel, was approved by the FDA in 2022.
CAR T-cell therapies are also available to treat other forms of blood cancer, including leukemia and lymphoma.
Generally, doctors only recommend CAR T-cell therapy for people with multiple myeloma who meet certain conditions. The FDA-approved indications differ by product:
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 several studies looking at the two FDA-approved CAR T-cell therapies.
The first small study of ide-cel found that most people who received this treatment had reduced cancer signs and symptoms.
In a second larger study of ide-cel called KarMMa, researchers found that CAR T-cell therapy had many beneficial effects for myeloma, including:
A third study, KarMMa-3, looked at ide-cel compared to traditional therapies among people who had already tried between two and four separate rounds of treatment. The study found an overall response rate of 71 percent for CAR T-cell therapy compared to a 42 percent response rate for standard treatments. After this study, the FDA approved the use of ide-cel earlier in the treatment process.
A series of studies called CARTITUDE researched the effects of cilta-cel. In CARTITUDE-4, researchers compared cilta-cel with a control group receiving combination therapies traditionally used to treat relapsed or refractory multiple myeloma.
Results showed an overall response rate of 85 percent among people treated with cilta-cel compared to 67 percent in the control group. The FDA expanded the indication for cilta-cel after these results were published.
However, CAR T-cell therapy has worked very well for many people with hard-to-treat myeloma, even when other treatments have failed. These therapies are still relatively new, and researchers continue to study their long-term effectiveness and safety.
Other CAR T-cell treatments are currently being studied in clinical trials. Some studies are focused on combining CAR T-cell therapy with immunomodulators to improve efficacy.
Researchers are also looking into ways to enhance CAR T-cell therapy to overcome treatment resistance and reduce side effects. The future of CAR T-cell therapy may also include personalized treatments targeted toward individual tumor profiles.
These new approaches to CAR T-cell therapy are still being studied and may become available in the future.
In the ide-cel clinical trials, CAR T-cell therapy caused side effects for nearly every participant. Most side effects happened within eight weeks of infusion. Researchers are continuing to study the safety of CAR T-cell therapy and may release additional information about this treatment in the future.
Before undergoing CAR T-cell therapy, people with myeloma should thoroughly discuss the risks and benefits of treatment with their oncology team. There are ways to manage many of CAR T-cell therapy’s side effects.
Cytokine release syndrome (CRS) is a condition that sometimes develops after CAR T-cell therapy.
CRS may cause flu-like symptoms, including fever, chills, fatigue, breathing problems, and confusion. When it’s severe, CRS can lead to organ failure and may become life-threatening.
Read more about CRS here.
CAR T-cell therapy may also affect the brain and cause neurological side effects. Symptoms of neurological toxicity may include:
CAR T-cell therapy can lead to some other common side effects, such as:
Carvykti also carries a boxed warning for immune effector cell-associated enterocolitis, a rare but serious condition that can cause severe or prolonged diarrhea, abdominal pain, and weight loss.
If you choose to try CAR T-cell therapy, talk to your doctor about possible side effects. Ask your healthcare team which side effects may be a sign of a more serious health problem.
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I had my CarT therapy in September 2021 I had no issues or side effects. It took awhile for my blood counts to come back to good statuses, but at 11 months and counting, I’m doing very well and am in… read more
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