CAR T-Cell Therapy

Overview

What is CAR T-cell therapy?

CAR T-cell therapy is a type of cancer therapy that uses a patient’s own modified white blood cells to kill cancer cells.

What types of cancer does CAR T-cell therapy treat?

Two CAR T cell therapies are currently available – axicabtagene ciloleucel (Yescarta®) and tisagenlecleucel (Kymriah®).

Yescarta® has been approved by the Food and Drug Administration (FDA) to treat adults with large B-cell non-Hodgkin lymphomas (including diffuse large B-cell lymphoma –DLBCL) whose cancer has returned or has not been fully successfully treated with at least two prior treatment regimens. Lymphoma is a cancer of the body’s immune system. Kymriah® is approved for children and adults up to age 25 with advanced acute lymphoblastic leukemia (cancer of the body’s blood-forming tissues).

Other CAR T-cell therapies are being developed for other blood cancers including chronic lymphocytic leukemia, other forms of lymphoma, and multiple myeloma.

Procedure Details

How does CAR T-cell therapy work?

The process begins by collecting blood from the patient with cancer. During this process, T cells are separated and removed from the blood and the remaining blood is returned to the body. This procedure is called leukapheresis or apheresis and is similar to the process of giving certain types of blood donations. T cells, which are a type of white blood cell of the immune system, are the body’s primary killing cells. They protect the body by destroying abnormal cells, including cancers.

Sometimes, however, T cells don’t recognize cancer cells or cannot fully destroy all of them in the body. To improve the cancer-killing ability of T cells, the next step is to genetically alter them. This is done in a special laboratory. The altered T cells now have special receptors on their surface. These new receptors, called chimeric antigen receptors (CAR), allow the T cells to better recognize cancer cells, become activated, and kill their target. These altered T cells are now called a chimeric antigen receptor (CAR) T cells. The CAR T cells are then grown in a special laboratory until millions are produced.

Car t-cell therapy process

Next, the patient receives a brief course of chemotherapy, which improves the chance that the new CAR T cells will be accepted and not attacked by the immune system when returned to the body. Finally, the CAR T cells are delivered back into the patient through an infusion into the patient’s bloodstream. Once in the body, the CAR T cells continue to multiply. The CAR T cells attach to a specific structure, called an antigen (most commonly a protein called CD19), on the surface of the targeted cancer cells. Once attached, the T cells become activated and release toxins that kill the cancer. The CAR T cells remain in the body for a long time after the infusion, helping to fight cancer if it returns and keep the patient in remission.

Car t-cells

How long does the patient remain in the hospital following CAR T-cell therapy?

Patients typically need to stay in the hospital one to one and one-half weeks after receiving CAR T-cell therapy. Length of stay depends on many factors including the patient’s response to treatment and the risk for side effects.

Risks / Benefits

What are the side effects of CAR T-cell therapy?

The most common side effects seen are:

  • Cytokine release syndrome, which is similar to flu-like symptoms (headache; fever; chills; severe nausea, vomiting, diarrhea; severe muscle or joint pain), shortness of breath, low blood pressure and fast heart rate. These symptoms are mild in most patients but can be serious and life threatening.
  • Neurologic events can also be experienced and can be serious in some patients. Neurologic events include encephalopathy (brain disease, injury, malfunction), confusion, aphasia (difficulty understand or speaking), drowsiness, agitation, seizures, loss of balance and altered consciousness.
  • Low white blood cell count (neutropenia)
  • Low red blood cell count ( Anemia )

Fortunately, most of the side effects can be managed with drugs or resolved on their own without the need for treatment. Ask your physician or care team about all the potential side effects. Call your doctor right away if you experience these or any other side effects.

What’s the success rate of CAR T-cell therapy for lymphoma?

Over 80 percent of patients who received Yescarta® in clinical trials experienced either a complete or partial response. (A complete response means there were no signs of cancer; partial response means there was some reduction in the extent of the cancer.)

Over 80 percent of children and young adults treated with Kymriah® in clinical trials had their cancer go into remission.

Data about the long-term success of these drugs continues to be collected.

Recovery and Outlook

What’s the outlook (the prognosis) for using CAR T-cell therapy for lymphoma and other blood cancers?

Early results of CAR T-cell therapy for treating lymphoma and other blood cancers are highly promising and exciting. Many patients whose blood cancers returned or in whom other standard treatments failed achieved complete success (no signs of cancer) with CAR T-cell therapy. However, to confirm the early success of this therapy, longer term trials that enroll larger numbers of patient are needed. Larger trials will also help further identify the side effects of this therapy and ways to best manage them.

Last reviewed by a Cleveland Clinic medical professional on 06/27/2018.

References

  • Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. (https://www.ncbi.nlm.nih.gov/pubmed?term=(%22The%20New%20England%20journal%20of%20medicine%22%5BJournal%5D%29%20AND%20Hill%20BT%5BAuthor%5D "The New England journal of medicine.") 2017 Dec 28;377(26):2531-2544. Accessed 7/02/2018.
  • National Institutes of Health. National Cancer Institute. With FDA Approval for Advanced Lymphoma, Second CAR T-Cell Therapy Moves to the Clinic. (https://www.cancer.gov/news-events/cancer-currents-blog/2017/yescarta-fda-lymphoma) Accessed 7/02/2018.
  • Leukemia & Lymphoma Society. Chimeric Antigen Receptor (CAR) T-Cell Therapy. (http://www.lls.org/treatment/types-of-treatment/immunotherapy/chimeric-antigen-receptor-car-t-cell-therapy) Accessed 7/02/2018.
  • National Institutes of Health. National Cancer Institute. CAR T cells: Engineering Patients’ Immune Cells to Treat Their Cancers. (https://www.cancer.gov/about-cancer/treatment/research/car-t-cells) Accessed 7/02/2018.
  • Novartis. Tisagenlecleucel (Kymriah). How Treatment May Help. (https://www.us.kymriah.com/acute-lymphoblastic-leukemia-children/about-treatment/how-treatment-may-help/) Accessed 7/02/2018.

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