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Immunotherapy is the use of medicines to help a person’s own immune system recognize and destroy cancer cells. Many types of immunotherapy are being studied for use against childhood leukemia, and some are now coming into use.

Chimeric antigen receptor (CAR) T-cell therapy

For this treatment, immune cells called T cells are removed from the child’s blood and genetically altered in the lab to have specific receptors (called chimeric antigen receptors, or CARs) on their surface. These receptors can attach to proteins on leukemia cells. The T cells are then multiplied in the lab and given back into the child’s blood, where they can seek out the leukemia cells and attack them.

Tisagenlecleucel (Kymriah)

This is a type of CAR T-cell therapy that targets the CD19 protein on certain leukemia cells. It can be used to treat childhood acute lymphoblastic leukemia (ALL) that has come back after treatment or that is no longer responding to treatment.

To make this treatment, T cells are removed from the child’s blood during a process called leukapheresis. Blood is removed through an IV line and goes into a machine that removes the T cells. The remaining blood then goes back into the body. This typically takes a few hours, and it might need to be repeated. The cells are then frozen and sent to a lab, where they are turned into CAR T cells and are multiplied. This process can take a few weeks.

For the treatment itself, the child typically gets chemotherapy for a few days to help prepare the body. Then the CAR T cells are infused into a vein.

In most children who have had this treatment, the leukemia could no longer be detected within a few months of treatment, although it’s not yet clear if this means that they have been cured.

Possible side effects

This treatment can have serious or even life-threatening side effects, which is why it needs to be given in a medical center that is specially trained in its use.

Cytokine release syndrome (CRS): CRS happens when T cells release chemicals (cytokines) that ramp up the immune system. This can happen within a few days to weeks after treatment, and can be life-threatening. Symptoms can include:

• High fever and chills
• Trouble breathing
• Severe nausea, vomiting, and/or diarrhea
• Severe muscle or joint pain
• Feeling dizzy or lightheaded

Nervous system problems: This drug can have serious effects on the nervous system, which can result in symptoms such as:

• Headaches
• Changes in consciousness
• Confusion or agitation
• Seizures
• Trouble speaking and understanding
• Loss of balance

Other serious side effects: Other possible side effects can include:

• Serious infections
• Low blood cell counts, which can increase the risk of infections, fatigue, and bruising or bleeding

It’s very important to report any side effects to the health care team right away, as there are often medicines that can help treat them.

Monoclonal antibodies

Antibodies are proteins made by the body’s immune system to help fight infections. Man-made versions of these proteins, called monoclonal antibodies, can be designed to attack a specific target, such as a protein on the surface of leukemia cells.

Blinatumomab (Blincyto)

Blinatumomab is a special kind of monoclonal antibody known as a bispecific T-cell engager (BiTE). It can attach to 2 different proteins at the same time. One part of blinatumomab attaches to the CD19 protein, which is found on B cells, including some leukemia cells. Another part attaches to CD3, a protein found on immune cells called T cells. By binding to both of these proteins, this drug brings the leukemia cells and immune cells together, which helps the immune system attack the leukemia cells.

This drug is used to treat some types of B-cell ALL in children. For example:

• It might be used as part of the second (consolidation) phase of treatment in some children with ALL.
• It might be used to treat ALL that comes back or that is no longer responding to other treatments.
• It might be used earlier in the course of treatment for some infants with ALL.

Blinatumomab is given into a vein (IV) as a continuous infusion over 28 days. This may be repeated after 2 weeks off. Because of certain serious side effects that occur more often during the first few times it is given, the child usually needs stay in the hospital for the first few days of at least the first 2 cycles.

The most common side effects are fever, headache, swelling of the feet and hands, nausea, tremor, rash, constipation, and low blood potassium levels. It can also cause low white blood cell counts, which increase the risk of serious infection.

This drug can also cause nervous system problems, such as seizures, trouble speaking or slurred speech, passing out, confusion, and loss of balance.

Some children might have serious infusion reactions (similar to an allergic reaction) while getting this drug. Symptoms can include feeling lightheaded or dizzy (due to low blood pressure), headache, nausea, fever or chills, shortness of breath, and/or wheezing. Your child will be given medicines before each infusion to help prevent this. 

Antibody-drug conjugates (ADCs)

These are monoclonal antibodies attached to chemo drugs. The antibody part acts like a homing device, bringing the chemo drug directly to the leukemia cells.

• Gemtuzumab ozogamicin (Mylotarg) can be used to treat some children with acute myeloid leukemia (AML).
• Inotuzumab ozogamicin (Besponsa) can be used to treat children with some types of B-cell ALL.

These medicines are described in more detail in Targeted Therapy Drugs for Childhood Leukemia.

Other types of immunotherapy are also being studied for use against leukemia.