Immunotherapy for Childhood Leukemia

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

For this treatment, immune cells called T cells are removed from the child’s blood through an IV line that goes into a machine during a process called leukapheresis. The remaining blood then goes back into the body. This typically takes a few hours, and it might need to be repeated.

The T cells are then 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. This process can take a few weeks.

For the treatment itself, the child typically gets chemo 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 is not yet clear if this means that they have been cured. Many children still undergo a stem cell transplant after CAR T-cell therapy.

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
• Low blood pressure
• Heart problems
• Kidney problems
• 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 count, which can increase the risk of infections, fatigue, and bruising or bleeding

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

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 proteins, this drug brings the leukemia cells and immune cells together, which helps the immune system attack the leukemia.

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 during treatment for some infants with ALL.

Blinatumomab is given into a vein (IV) as a continuous infusion over 28 days. Because of certain serious side effects, such as cytokine release syndrome (see below) that may occur during the first few times it is given, the child usually needs to stay in the hospital for the first few days of the infusion.

Possible side effects

Cytokine release syndrome (CRS): CRS happens when the body releases chemicals (cytokines) that ramp up the immune system. Symptoms can include:

• High fever and chills
• Trouble breathing
• Low blood pressure
• Heart problems
• Kidney problems
• 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

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, or wheezing. Your child will often be given medicines before the infusion starts to help prevent this.

Inotuzumab ozogamicin is an antibody-drug conjugate (ADC) used in some children with B cell ALL. This treatment is a monoclonal antibody attached to chemo drugs. The antibody part acts like a homing device, bringing the chemo drug directly to the leukemia cells.

This drug is described in more detail in Targeted Therapy Drugs for Childhood Leukemia.

Rituximab is a monoclonal antibody that targets a protein on many B cells, called CD20. When rituximab binds to leukemia cells with this protein, it triggers the cells to die. Some people with B cell ALL, especially Burkitt leukemia, may get rituximab as a part of their treatment plan.

Rituximab is given into a vein (IV).

Possible side effects

Because rituximab targets any cells with the CD20 protein, healthy B cells are also affected by the treatment. This can lead to a weaker immune system and lower levels of antibodies, sometimes for months to years after treatment. Other side effects of rituximab can include fevers, low energy, headaches, upset stomach, muscle or joint aches, flushing, and night sweats.

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.

A rare and severe blistering skin rash with mouth sores, called Stevens-Johnson syndrome, has also been seen after rituximab.