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When your body doesn’t respond to standard lymphoma treatments, it can feel discouraging. Chimeric antigen receptor (CAR) T-cell therapy is a type of immunotherapy that may offer another option. Doctors collect some of your immune cells and train them to spot lymphoma cells. Then they put the cells back into your body to help fight the cancer. For some people, CAR T-cell therapy can help when other treatments have not worked.
In this article, we’ll explain how CAR T-cell therapy works, including how T cells are collected, altered, and infused back into the body. We’ll also review some CAR T-cell therapies approved by the Food and Drug Administration (FDA) to treat lymphoma. Finally, we’ll discuss the possible benefits and risks of this approach, including the most common side effects.
CAR T-cell therapy is a form of cellular therapy, which means it uses your T cells to fight cancer. T cells are a type of white blood cell that help protect your body from infections. In lymphoma, cancer starts in B or T lymphocytes that grow out of control. CAR T-cell therapy gives your T cells new tools so they can better find and attack lymphoma cells.
To make CAR T cells, scientists place a special receptor called a chimeric antigen receptor on the surface of your T cells. This receptor helps the cells find and attack cancer cells that your body can’t fight well on its own.
CAR T-cell therapy is approved to treat several types of large B-cell lymphomas (LBCL), including:
CAR T-cell therapy may be used for people with large B-cell lymphomas whose cancer has come back after treatment or hasn’t responded well to earlier care. For example, many people who receive CAR T-cell therapy have already tried chemotherapy, targeted drugs, or a stem cell transplant, but still need another option.
Doctors may also consider CAR T-cell therapy for people who have fast-growing lymphoma or who can’t receive more intensive treatment options. To qualify, you’ll need to be healthy enough for the infusion and the recovery period. Your care team will evaluate your overall health, how your lymphoma has progressed over time, and whether CAR T-cell therapy offers the best chance to control the disease.
From start to finish, the process of getting CAR T-cell therapy can take three to six weeks. During this time, your care team will stay in close contact to make sure each step goes smoothly. Below is a simple overview of how CAR T-cell therapy turns your own T cells into strong cancer-fighting cells.
The first step is called leukapheresis, also known as apheresis. You’ll be hooked up to a machine that collects your blood through a small tube and gently separates your T cells. The rest of your blood is returned to your body. This is often done as an outpatient visit and usually takes a few hours, so you can go home the same day. Afterward, your T cells are sent to a lab for the next step.
Next, scientists add a gene that helps your T cells grow a chimeric antigen receptor. This special protein on the T cell’s surface helps it find cancer cells. This new receptor helps the T cells recognize markers on lymphoma cells.
Many of these cancers carry markers (special protein tags), including one called CD19 that CAR T cells can easily recognize. Once the modified T cells have the CAR molecule, they’re better prepared to seek out and attack cancer cells.
Once the T cells are changed, they’re grown into millions of new CAR T cells. This process usually takes a few weeks. While you wait, your care team keeps track of the progress and prepares you for the next stage of treatment.
Before your CAR T-cell infusion, you’ll get a short course of low-dose chemotherapy. This step is called lymphodepletion, or lymphodepleting therapy. It lowers the number of lymphocytes in your body and makes room for the CAR T cells to work. It can also help keep your body from rejecting the new cells.
When your CAR T cells are ready, they’re returned to you through an intravenous (IV) infusion. Once inside your bloodstream, the cells travel through your body, find the lymphoma cells, and attack them. They can continue working for weeks or even months after the infusion, helping your body stay in the fight against cancer.
There are three FDA-approved CAR T-cell therapies available for people with large B-cell lymphoma that is relapsed or refractory. Relapsed means the lymphoma came back after treatment. Refractory means the lymphoma didn’t improve with treatment. Each CAR T-cell therapy targets CD19, a marker found on many lymphoma cells, but they differ in how and when they’re used.
Axicabtagene ciloleucel (Yescarta) was approved in 2017 for adults with certain LBCLs that haven’t responded to at least two earlier treatments. This includes DLBCL, high-grade B-cell lymphoma, and primary mediastinal large B-cell lymphoma. It is now also approved for some people whose lymphoma is refractory to first-line treatment or relapses within 12 months.
Lisocabtagene maraleucel (Breyanzi) was approved in 2021 for adults with relapsed or refractory LBCL after at least two earlier treatments. It is now also approved for some people whose lymphoma doesn’t respond to first-line treatment or returns within 12 months. Breyanzi uses a defined dose of two types of T cells: CD4⁺ and CD8⁺ T lymphocytes, which may help doctors better control how the therapy is delivered.
Tisagenlecleucel (Kymriah) was first approved in 2017 for children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia. In 2018, it was also approved for adults with relapsed or refractory LBCLs who have already received two or more previous treatments.
One of the biggest benefits of CAR T-cell therapy is that it can work well and last, even when other treatments haven’t helped. In clinical trials and large studies, CAR T cells have helped people with LBCL, including people who are older or have more advanced disease.
Another key benefit is that CAR T cells can keep working after the infusion. They can keep looking for lymphoma cells and destroying them, which may help some people stay in remission for a long time. CAR T-cell therapy may also work even after other immune system-based treatments have been tried, giving another option when the cancer is hard to control.
CAR T-cell treatment is powerful, but it can also cause side effects as your immune system becomes more active. Two of the main reactions your care team watches for are cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS).
CRS happens when the immune system releases many signaling proteins, called cytokines, all at once. This can lead to high fever, chills, low blood pressure, and trouble breathing. In most people, CRS is mild to moderate and improves with treatment such as fluids, oxygen, or medicines that calm the immune response. More serious CRS can happen, which is why you’ll be monitored very closely.
ICANS affects the brain and nervous system. Symptoms may include confusion, headache, trouble speaking, or feeling very sleepy. With proper care, these symptoms are usually temporary.
Other possible side effects of CAR T-cell therapy can include:
Your healthcare team will schedule follow-up appointments to monitor you closely after CAR T-cell therapy. If you have any new or worsening symptoms within the first few weeks after your infusion, reach out to your doctor right away.
On MyLymphomaTeam, people share their experiences with lymphoma, get advice, and find support from others who understand.
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