Published on March 12, 2021
Why Do Kids with ALL Have a Better Tolerance for CAR T-Cell Therapy?
Acute lymphoblastic leukemia (ALL) is a relatively rare disease of immune cells (B cells or T cells) affecting approximately 6,000 people annually. It’s the most common subtype of leukemia among children. Depending on the patient’s age and treatment, outcomes can vary. For example, adults and children with ALL have different CAR T-cell therapy experiences and outcomes. Children often fare better, but why?
“On one hand it is not truly known, but we do know that adults have more side effects,” said Dr. Nitin Jain, Associate Professor in the Leukemia Department at the University of Texas MD Anderson Cancer Center. Dr. Jain treats adult patients with ALL.
Side Effects Include Cytokine Release Syndrome, Neurotoxicity
CAR T-cell therapy treats ALL by using a patient’s own immune cells which are removed and re-engineered in a laboratory. A few short weeks later, these modified cells are put back into the patient, usually after the patient has received chemotherapy in the interim. The hematology/oncology team will then monitor the patient closely to look for any side effects in the days immediately following treatment.
The two main adverse effects of CAR T-cell therapy are cytokine release syndrome (CRS) and neurotoxicity (affecting brain and nervous system function). CRS is also known as a cytokine storm: when the body starts making cytokines that can cause severe symptoms (a cytokine is a type of protein that affects the immune system).
Grade 1, the least worrying level of CRS, is categorized by a fever, which is a pretty universal side effect among patients who undergo CAR T-cell therapy. It’s treatable and often goes away in a few days. More serious CRS symptoms include low blood pressure and low oxygen in the blood, requiring oxygen support and IV fluids/medications to improve blood pressure. Some patients may require ICU care to help manage these severe symptoms. Medications such as tocilizumab (Actemra) and steroids are frequently prescribed, which is great because they go to work quickly.
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinical and newer name for the neurotoxicity that can occur in the days to weeks following CAR T-cell therapy. People often experience brain fog, forgetfulness and that tip-of-the-tongue experience that happens to some of us when reaching for a name to a face that’s right in front of us. This side effect is common, but fortunately, it’s reversible in the majority of patients.
“Those side effects are more common in adults than in children,” Dr. Jain said. “Kids tolerate treatment well, in general.”
Other complications from CAR-T cell therapy include low white blood cell counts and the risk of infection.
Current Adult Clinical Trials Could Bridge the Gap
Currently, there is one CAR T-cell therapy available for childhood ALL. It’s called tisagenlecleucel (Kymriah) and was approved by the FDA in 2017 for children and young people up to the age of 25 who have been diagnosed with B-cell ALL that is refractory (does not respond to treatment) or has relapsed at least twice.
Tisagenlecleucel is not yet approved for patients with ALL who are older than 25 because adults were not included in early clinical trials. Concurrent studies at various academic centers with different CAR-T products are now investigating CAR-T in adult ALL. The data is not yet mature, but Dr. Jain is hopeful that perhaps by the next annual meeting of the American Society of Hematology (ASH), more data will be available.
Dr. Jain suggests that perhaps a combination of CAR T-cell products that target more than one antigen, such as CD19 and CD22, or CD19 and CD20, may improve the efficacy and toxicity of this therapy.
“These are the kinds of clinical trials happening right now for our adult ALL patients,” he said.
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- Novartis receives first ever FDA approval for a CAR-T cell therapy, Kymriah(TM) (CTL019), for children and young adults with B-cell ALL that is refractory or has relapsed at least twice. News Release. Feb. 2021.
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