Who may benefit from CAR T-cell therapy?
CAR T-cell therapy is not a first-line treatment for cancer. It is used when cancer has either returned after treatment or hasn't responded to standard treatments.
For pediatric patients, the Food and Drug Administration (FDA) has approved a specific CAR T-cell therapy – tisagenlecleucel (Kymriah) – to treat acute lymphoblastic leukemia (ALL) arising from B cells. It is approved for children and young adults up to age 25.
More than 80% of children with B-cell ALL are cured by intensive chemotherapy. However, for children whose cancer doesn't respond or recurs, CAR T-cell therapy offers another option.
For young adults (age 18 and older) with B-cell non-Hodgkin's lymphoma or B-cell ALL, UCSF Benioff Children's Hospitals offer two CAR T-cell therapies, axicabtagene ciloleucel (Yescarta) and brexucabtagene autoleucel (Tecartus).
CAR T-cell therapy has also shown remarkable promise for certain B cell–driven autoimmune diseases, such as systemic lupus erythematosus. UCSF is conducting several clinical trials to test its use in children, adolescents and young adults with these conditions.
How do CAR T cells work?
T cells are immune cells that find and fight diseases, such as infections, in the body. CAR T-cell therapies are designed to harness this power to fight cancer or autoimmune disease.
CAR T cells are created by genetically engineering the patient's T cells to make a protein called a chimeric antigen receptor. This receptor binds to a specific protein (called an antigen) on the surface of the patient's cancer cells, like a key fitting into a lock. The CAR T cells then destroy the cancer cells.
Different cancers have different antigens, so each CAR T-cell therapy is customized to the patient's specific cancer.
Evaluation for CAR T-cell therapy
A pediatric oncologist will work with your family to determine whether CAR T-cell therapy is a suitable option for your child.
Since the CAR T cells are tailor-made for each patient, it takes about four to eight weeks to produce and administer the therapy. Your child must be healthy enough to wait that long. The oncologist may need to run tests to determine their eligibility and ability to undergo the treatment.
In most cases, patients receive bridging therapy (treatments to control their cancer until the CAR T cells are ready).
Procedure for CAR T-cell therapy
CAR T-cell therapy occurs in three main stages: T-cell collection, the modification process and infusion.
Step 1: Leukapheresis (T-cell collection)
Your child will undergo a procedure called leukapheresis to collect the T cells for modification. Using intravenous (IV) lines or a central line (a catheter placed in a large vein above the heart), your child is connected to a machine that draws blood from a vein, separates out the T cells, and returns the remaining components to their bloodstream. The T cells are then sent to a highly specialized manufacturer for genetic modification.
Leukapheresis is typically an outpatient procedure, meaning your child can go home the same day, although some patients need to stay in the hospital for a day.
Step 2: Genetic modification
At the CAR T-cell manufacturer, your child's T cells are genetically modified to include CARs that match the antigens on their cancer cells. The manufacturer then grows millions of the modified T cells for your child's treatment. This process takes about three to six weeks.
Your child may receive bridging therapy while waiting for the modified cells to be ready.
About five days before the CAR T-cell infusion, your child will undergo a treatment known as lymphodepleting chemotherapy. This treatment uses specific chemotherapy medicines to reduce the number of immune cells in the body and make room for the modified cells (the CAR T cells).
Lymphodepleting chemotherapy can have side effects, including nausea, vomiting, low blood cell counts (requiring transfusions of red blood cells or platelets), and an increased risk of infection. Talk to your child's doctor if you have any concerns after lymphodepleting chemotherapy.
Step 3: Infusion
Once the modified T cells are ready, they're shipped back to UCSF and given to your child as an IV infusion in the hospital or clinic. The CAR T-cell infusion usually takes 30 to 60 minutes, depending on your child's size.
Short-term side effects of CAR T-cell therapy
While CAR T-cell therapy can be very effective, it may have serious and even life-threatening side effects. Children experiencing significant side effects are admitted to the Pediatric Intensive Care Unit for around-the-clock monitoring and treatment.
If your child experiences any of the treatment side effects described below, contact their medical team right away.
Cytokine release syndrome (CRS)
Certain immunotherapy treatments, including CAR T-cell therapy, can trigger the body to release large amounts of cytokines (proteins that can stimulate or calm the immune system) into the bloodstream. This condition is called cytokine release syndrome (CRS).
Signs of CRS include:
- Difficulty breathing
- Dizziness, lightheadedness or headaches
- Fatigue
- Fever and chills
- Low blood pressure
- Muscle or joint pain
- Nausea, vomiting or diarrhea
- Rapid heartbeat
Nervous system effects (ICANS)
Certain immunotherapies, including CAR T-cell therapy, can cause a group of neurological side effects called immune effector cell–associated neurotoxicity syndrome, or ICANS. Symptoms may include:
- Confusion
- Headaches
- Loss of balance
- Seizures
- Shaking or twitching (tremors)
- Trouble with speech and comprehension
Other possible side effects
Additional side effects of CAR T-cell therapy may include:
- Allergic reactions to the infusion
- Decreased blood cell counts
- Easy bruising or bleeding
- Low potassium, sodium or phosphorus levels in the blood
- Severe infections (due to a weakened immune system)
Although it's rare, some patients experience long-term complications from CAR T-cell therapy. Your child's doctor will discuss these risks with you.
