How does CAR-T cell therapy work?
Kaylyn White was an active and happy 12-year-old until bone and joint pain stopped her in her tracks. When she started losing weight and experiencing random nosebleeds, her mother knew something was wrong.
“We saw the energy drain out of her,” says Lesley White. “She was in so much pain.”
After several visits to local doctors, including referrals to a physical therapist and rheumatologist, a complete blood count test revealed Kaylyn’s white blood cells were extremely high. She was rushed to the emergency room at MD Anderson Cancer Center and soon after was diagnosed with high-risk acute lymphoblastic leukemia (ALL).
Kaylyn received her first dose of chemotherapy just days before Christmas 2017. After four weeks of treatment, a bone marrow evaluation showed her leukemia was resistant to chemotherapy. Doctors classified her disease as refractory (treatment resistant) B-cell acute lymphoblastic leukemia.
Just months before Kaylyn’s diagnosis, the Food and Drug Administration approved a groundbreaking new type of cancer treatment known as CAR T. This technology harnesses the power of patients’ immune cells – which are extracted from them, re-engineered in a lab, and then pumped back into the body – to kill aggressive blood cancers. The treatment, tisagenlecleucel, was hailed as a major advance in treating patients 25 years of age and younger who, like Kaylyn, were diagnosed with refractory B-cell ALL.
While Kaylyn’s cells were harvested – which typically takes four to six weeks – she remained in the hospital and continued to receive chemotherapy so her cancer wouldn’t spread. Just 30 days after being infused with her amped-up T cells, tests showed she had no evidence of disease, and her leukemia was in complete remission.
“It was a blessing to be able to have access to this procedure,” Lesley says. “This therapy did its job and the doctors helped save our daughter’s life.”
For patients, like Kaylyn, whose cancer does not respond to standard treatment, CAR T-cell therapy may be the last resort. MD Anderson Children’s Cancer Hospital began offering the treatment to pediatric in March 2018, and Kaylyn is one of five pediatric patients to receive the therapy so far.
“In my opinion, this therapy is the most phenomenal thing that has happened in leukemia since chemotherapy,” says Kris Mahadeo, M.D., section chief and medical director of Pediatric Stem Cell and Cell Therapy.
Comprehensive treatment guidelines released
Almost one year after the FDA approved CAR T-cell therapy for children with acute lymphoblastic leukemia, researchers at MD Anderson and the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) published CAR T-cell therapy pediatric treatment guidelines. The guidelines outline lessons learned by leading experts in various fields to identify early signs and symptoms of treatment-related toxicity and detail ways to manage it.
“While CAR T-cell therapy has cured 90 percent of patients that standard therapy would not have saved, safe administration requires trained staff across a variety of disciplines,” Mahadeo says. “It’s important that all providers from a variety of fields are trained to recognize toxicities to ensure prompt treatment to save lives. Most of the toxicities, if caught early, are treatable.”
CAR T-cell therapy has resulted in some unique and severe toxicities that can affect the cardiac, respiratory and neurologic systems. Medical vigilance of a diverse multi-disciplinary team, as well as the proper clinical infrastructure, is required to ensure the best outcome, Mahadeo says.
Researchers from MD Anderson’s CAR T-cell-therapy-associated Toxicity (CARTOX) program collaborated with PALISI researchers, which brought together experts from many areas, including pediatric intensivists, pharmacy, neurology, and translational immunotherapy research. Together, they produced guidelines designed to improve patients’ experiences and outcomes.
Though the guidelines were developed in response to the FDA approval of the first CAR T-cell therapy for ALL pediatric patients, Mahadeo says the guidelines will positively impact future CAR T-cell therapies.
MD Anderson researchers hope to use this therapy to treat other forms of cancer. Mahadeo and his team also are exploring CAR T cells that target fungal and viral infections.