CAR T-cell therapy

Chimeric antigen receptor (CAR) T-cell therapy is a kind of immunotherapy, which uses the body’s immune system to fight cancer. It involves changing some of the immune cells in the patient's body so they can better fight and kill cancer cells. It may be a treatment option for patients who have certain blood cancers or multiple myeloma and other therapies aren’t working.

T-cells and B cells are the two main types of white blood cells, called lymphocytes, that help the immune system fight off invaders. T-cells do this by identifying proteins on the surface of invading cells. These proteins are called antigens. T-cells have receptors that latch onto the antigens and destroy the invading cells. The T-cell has to have the right receptor—one that fits the antigen on the invading cell—to latch on and destroy it.

Cancer cells have antigens, and CAR T-cell therapy re-engineers the body’s T-cells to add receptors that latch on and destroy the cancer cells. CAR T-cell therapy removes T-cells from the blood and changes them in the lab by inserting genetic information that tells them to make the receptors for specific types of cancer cells. The re-engineered T-cells are then put back in the patient's body so they can identify and kill the cancer cells.

This article will cover:

• FDA-approved CAR T-cell therapies
• CAR T-cell therapy process
• How to prepare for CAR T-cell therapy
• Potentially serious CAR T-cell side effects
• CAR T-cell therapy recovery
• What happens if CAR T-cell therapy fails?
• CAR T-cell therapy cost

FDA-approved CAR T-cell therapies

CAR T-cell therapy has been available since the U.S. Food and Drug Administration (FDA) first approved the therapy in 2017. To date, the FDA has approved six versions of CAR T-cell therapy to treat several types of blood cancer, including:

• Acute lymphoblastic leukemia
• Multiple myeloma
• Certain types of non-Hodgkin lymphoma 

Different types of cancer cells have different antigens, so each version of CAR T-cell therapy contains receptors that are engineered for a specific type of cancer cells. CAR T-cell therapy may also be used to treat mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and follicular lymphoma.

CAR T-cell therapy process

It may take several weeks to undergo CAR T-cell therapy.

Process for collecting T-cells

In the first step, doctors remove T-cells from the blood, then connect two intravenous (IV) lines to the body, usually in the arms. One line removes the blood, while the other returns it to the patient's body. After it is removed, the blood passes through a machine that separates out the white cells (which include T-cells) before returning the blood to the body. In some cases, a patient may have a central line or catheter leading into the heart’s main artery instead of two IV lines.

The process of collecting the cells is called leukapheresis. It can take two or three hours. The patient may experience muscle spasms, numbness or tingling because of low calcium levels, which may be treated by replacing the calcium through an IV or by mouth.

Creating CAR T-cells

Following the white cell collection process, the T-cells are separated and then they're altered in a laboratory. During the alteration process, the gene for the specific receptor is added to the cells, turning them into CAR T-cells. Over a period of time that may span multiple weeks, the cells multiply until the care team determines that there's an adequate number for the CAR T-cell therapy.

CAR T-cell treatment

Before the T-cells are returned to the body, chemotherapy may be used to reduce accompanying immune cells. However, the care team typically does not use a strong dose of chemotherapy during this process, because CAR T-cell therapy is more effective when some cancer cells remain for them to target.

Once back in the body, the T-cells begin reproducing and increasing their attack.

How to prepare for CAR T-cell therapy

Patients should arrange for a ride to treatment, and they’ll likely be staying in a hospital afterward. Patients may need to avoid driving, operating heavy equipment or other potentially risky activities for a few weeks, due to potential side effects. The care team will schedule follow-up visits with lab tests, imaging and exams.

Potentially serious CAR T-cell side effects

While it’s provided new hope for some patients, CAR T-cell therapy also has limitations.

CAR T-cell therapy may cause potentially serious or even life-threatening side effects. One such side effect is called cytokine release syndrome (CRS), which happens when CAR T-cells release lots of chemicals called cytokines in the blood. Cytokines help ramp up the immune system, but they also cause inflammation. Symptoms of CRS range from flu-like symptoms to organ failure and even death. In mild cases, patients may experience:

• Fever
• Headache
• Fatigue
• Body aches
• Vomiting
• Diarrhea
• Rash

In serious cases, blood pressure may drop and fever may increase, and some patients may have severe inflammatory reactions, such as:

• Irregular heartbeat (arrhythmia) and other cardiovascular problems, including possible heart failure
• Liver and kidney failure
• Fluid in the lungs (pulmonary edema) and lung failure

The care team will monitor patients for CRS. Severe cases may be treated with a drug called tocilizumab.

Some patients also have side effects that affect the nervous system, or neurological side effects. These may include:

• Confusion and disorientation
• Trouble speaking or understanding
• Tremors or seizure-like activity
• Lack of awareness
• Loss of balance

The care team will watch for these neurological side effects, too. They may go away in a few days. If they don’t or if they’re severe, talk to the doctor about available treatments for these side effects.

Other possible side effects of CAR T-cell therapy include:

• Allergic reaction to the infusion
• A weakened immune system, which raises risk of infection
• Low blood cell levels, which increases risk of fatigue, bruises and bleeding
• Changes in blood levels of minerals, including potassium, phosphorus and sodium

Car T-cell therapy recovery

Following CAR T-cell therapy, the patient may need to remain hospitalized for up to two weeks while the care team monitors his or her treatment response and manages side effects that may occur.

The care team may ask patients to remain near the treatment facility for up to a month following infusion to continue monitoring for side effects and evaluating the response to the CAR T-cell therapy.

What happens if CAR T-cell therapy fails?

In some cases, the cancer may not respond well to treatment, or the cancer may recur—or come back—later on. There are several reasons why CAR T-cell therapy may fail:

• The cancer cells may stop making the antigen targeted by the therapy, which means the T-cells that were engineered for that specific antigen won’t work. This is called antigen loss.
• The CAR T-cells may stop destroying cancer cells due to a process called T-cell exhaustion.
• The CAR T-cells may not multiply, which will prevent them from targeting all of the cancer cells.
• The cancer cells may mutate, which means the T-cells can no longer identify the antigen they were programmed to destroy.

If CAR T-cell therapy is unsuccessful, the patient and his or her care team will work together to evaluate next steps, which varies from patient to patient.

CAR T-cell therapy cost

The cost of CAR T-cell therapy is high, and some estimates indicate it could top $1 million if side effects occur requiring extensive treatment. Medicare and Medicaid both cover CAR T-cell therapy under very strict guidelines, and some private insurers cover the treatment as well. 

To defray costs on the patient’s end, it’s essential that the care team works with insurers up-front to evaluate payment guidelines and get preapprovals prior to the procedure. The hospital can also assist the patient in finding local places to stay, if necessary, since many patients are asked to remain near the facility following the procedure to monitor for side effects.