CAR T-Cell Therapy

Overview

Chimeric Antigen Receptor (CAR) T-cell therapy enhances the efficiency of T-lymphocytes (T-cells) in combating cancer. While long-term data collection is ongoing, CAR T-cell therapy is showing promise as a treatment for various blood cancers.

T-cells are a type of white blood cell in your immune system responsible for monitoring proteins called antigens to detect potential invaders like cancer cells or other abnormal cells. These antigens are found on the surfaces of these intruder cells. Similar to an antivirus program on a computer, T-cells have unique proteins called receptors that allow them to identify and block  intruders when they encounter antigens. In this way, T-cells act as the security squad of your immune system, eliminating intruder cells.

However, intruder antigens have their own defense mechanism – they can change their identity to avoid detection by T-cells. CAR T-cell therapy ensures that T-cells can overcome these defenses and disguises used by the antigens of the invading cells.

Reasons for undergoing the procedure

A number of CAR T-cell therapies have been licensed by the US Food and Drug Administration (FDA) for patients with specific blood cancers that are not responsive to chemotherapy or other treatments. This therapy is also employed in the treatment of individuals with recurrent blood cancer after prior successful treatments.

Specialized programs known as Risk Evaluation and Mitigation Strategies (REMS) are used to provide CAR T-cell treatment. REMS guarantees that doctors are qualified to provide the therapy and are skilled in handling any potentially dangerous side effects.

Types of cancers are treated by this procedure

The following details on the cancers currently being treated with CAR T-cell therapy:

B-cell Acute Lymphoblastic Leukemia (ALL)

White blood cells or immature B lymphocytes are impacted by this cancer while they are developing in your bone marrow. Usually, doctors treat it with a bone marrow transplant and chemotherapy.

CAR-T cell medications approved by the FDA are

• Brexucabtagene autoleucel
• Tisagenlecleucel. This medication is utilized to treat ALL in children and young adults.

B-cell non-Hodgkin lymphoma

Diffuse Large B-cell Lymphoma (DLBCL), follicular lymphoma with DLBCL, and high-grade B-cell lymphoma are among the forms of B-cell non-Hodgkin lymphoma. Stem cell transplantation, monoclonal antibodies, and chemotherapy are the usual treatments used by providers for these diseases.

CAR-T cell medications approved by the FDA are:

• Axicabtagene Ciloleucel
• Tisagenlecleucel
• Lisocabtagene maraleucel

Primary mediastinal large B-cell lymphoma.

A CAR-T cell medication approved by the FDA is Axicabtagene ciloleucel.

Mantle cell lymphoma

This particular kind of non-Hodgkin lymphoma begins in the B lymphocytes in your body. Stem cell transplantation and chemotherapy are the usual treatments used by doctors.

A CAR-T cell medication approved by the FDA is Brexucabtagene autoleucel.

Multiple myeloma

This is a malignancy of the cells that produce antibodies, called plasma cells. Stem cell transplantation, targeted therapy, or chemotherapy are the methods used by doctors to treat this illness.

CAR-T cell medications approved by the FDA are: Idecabtagene vicleucel and Ciltacabtagene autoleucel

Scholars are examining the potential benefits of CAR T-cell treatment for patients with non-small cell lung, brain, or breast cancers.

Risks

CAR T-cell therapy has its limitations, and it may not always successfully eliminate cancer cells as intended. In certain cases, despite the initial effectiveness of the treatment, cancer can reappear or persist. Among the possible causes of CAR T-cell therapy’s failure are:

• T cells with altered genetic instructions produce CARs and other molecules.These cells are known as CAR T-cells. T-cells cannot locate and eliminate cancers until the newreceptors are activated or started up. Without that, CAR T-cells are unable to function.
• After entering your body, CAR T-cells should proliferate. If they don’t, it’s possible that insufficient cancer cells will be found and eliminated to prevent the cancer from spreading.
• CAR T-cells can occasionally just quit eliminating cancer cells. It is referred to as T-cell exhaustion when this occurs. T-cell exhaustion may be connected to transcription factors, which are proteins that aid in turning on and off genes, according to research.
• Cancer cells have the ability to mutate or alter, losing the antigen that CAR T-cells were designed to recognize.

Common CAR T-cell therapy side effects

CAR T-cell therapy contains adverse effects that can pose a serious risk to life, just like most cancer treatments. Neurological issues and cytokine release syndrome are the two most typical side effects.

Cytokine release syndrome

After your CAR T-cells have been given to you and have begun to grow and kill cancer cells, you may have cytokine release syndrome, or CRS. Chemicals called cytokines activate your immune system. Your immune system may react to the activation of your CAR T-cells by flooding your circulation with copious amounts of cytokines. CRS typically manifests in the first week or two following treatment.

Cytokine release syndrome symptoms

You could feel as though you have the flu if you have this syndrome. Symptoms of CRS include:

• High fever and chills
• Dizziness
• Headaches
• Nausea, vomiting and diarrhea
• Feeling exhausted
• Increased heart rate

Neurological risks of CAR T-cell therapy

Your nervous system may be impacted by CAR T-cell therapy, leading to symptoms that appear in the initial weeks following treatment. You should plan to refrain from driving or using machinery for eight weeks following your treatment because some symptoms may make it difficult for you to do those things. Symptoms of neurological disorders include:

• Headache
• Confusion
• Agitation
• Seizures
• Tremors
• Twitching
• Losing balance
• Speech problem

Before the procedure

You will go through a battery of tests to make sure you are healthy enough for CAR T-cell therapy before your T-cells are harvested. These examinations could consist of:

• Blood counts
• Infection tests
• Echocardiogram
• Pulmonary function tests
• Kidney and liver function test
• Computed Tomography (CT) or Positron Emission Tomography (PET)/CT imaging to check the disease location
• Magnetic Resonance Imaging (MRI) to ascertain whether the brain has been affected by your illness
• Spinal tap to ascertain whether the sickness has affected your central nervous system
• Bone marrow tests
• Biopsy

Emotional and Financial Concerns

If you’re facing emotional challenges related to your condition, you have the option to arrange a session with either a social worker or a psychologist. The social worker will also discuss the importance of your designated caregiver, whether it’s a family member or a friend. To help you gain a better understanding of what to anticipate both before and after treatment, you may receive an invitation to participate in a workshop tailored for both caregivers and recipients of CAR T-cell therapy.

In the event that your treatment center is located far from your home, you can also schedule a meeting with a financial counselor to review strategies for managing expenses. This may include discussing incidental costs such as parking, meals, transportation, and accommodations.

During the procedure

CAR T-cell process

Gathering your white blood cells is the first step in the CAR T-cell process. Here is a detailed explanation:

• A catheter is inserted by your doctor in a vein in your neck or under your collarbone.
• They attach the catheter to a device that will processyour blood, remove your white blood cells, and then give you back your plasma and red blood cells. Leukapheresis is the term for this procedure.
• After that, an inactive virus is inserted by your doctor to give your T-cells new genetic instructions.
• Equipped with new genetic instructions, your T-cells begin manufacturing CAR and molecules.
• The receptors land on the surface of your T cells. The molecules are found inside your T-cells, where they function as messengers to maintain T-cell activity.
• Providers take the tiny batch of CAR T-cells and encourage them to expand and multiply until there are enough CAR T-cells to efficiently target cancer cells in your body. Until the time comes for you to receive them, your new cells are frozen and kept.
• Chemotherapy will be required before to the delivery of your new cells in order to prevent immune system rejection. Your infusion of fresh cells will come after your chemotherapy. It is likely that you will require hospitalization for this partof your care. However, receiving your new cells might not require a hospital stay. Should that be the case, your doctor will keep a careful eye on both the procedure and your progression.
• Your CAR T-cells’ receptors will recognize the cancer cells once they enter your circulation and attach themselves to the antigens, or proteins, present in cancer cells. Your cells then eradicate the cancerous cells.
• Your CAR T-cells continue to grow and are able to search for any new cells with the target antigen.

After the procedure

Typically, patients need to spend approximately one to two weeks in the hospital to allow their doctors to manage potential side effects and closely monitor their response to the treatment. However, in some cases, your CAR T-cells can be administered without the need for a hospital stay. If this is the situation, your doctor will still closely oversee the procedure and your progress. If you do encounter any side effects, you may need to return to the hospital to complete your treatment.

Outcome

CAR T-cell therapy can lead to severe, and in some cases, even life-threatening side effects. Due to these potential risks, patients undergoing this treatment are generally mandated to stay in the hospital for several days, allowing doctors to closely monitor and address any side effects that may arise.

It is strongly recommended that you arrange for continuous, around-the-clock support from a caregiver during the initial month following the therapy. Furthermore, it’s advisable to secure accommodations within a short driving distance from your treatment center. Additionally, for a period of two months following the treatment, you should plan for someone to provide transportation for your needs.