Norton Children’s Cancer Institute, affiliated with the UofL School of Medicine, now offers CAR-T immunotherapy treatment for children who have difficult-to-treat acute lymphoblastic leukemia (ALL). Norton Children’s Cancer Institute is the only pediatric cancer program in Kentucky approved as a provider site for CAR-T immunotherapy.

CAR-T works by reprogramming the patient’s own T cells so they express on their cell surface a special protein called chimeric antigen receptor, which enables the T cells to find and kill cancer cells. In 2018, a CAR-T treatment was approved by the Food and Drug Administration (FDA) for pediatric patients whose ALL has relapsed or was refractory with traditional leukemia treatments. Norton Children’s has been approved by the manufacturer to offer this treatment to children who need it.

According to William T. Tse, M.D., Ph.D., director of the Norton Children’s Cancer Institute Pediatric Blood and Marrow Transplant Program, this means these ALL patients and their families will be able to stay close to home for this groundbreaking immunotherapy treatment.

“Most of the patients who need this treatment are our own patients who have received treatment from us previously. Now, these patients can stay with us and avoid having to travel long distances to other institutions to receive CAR-T therapy. They’re familiar with our doctors. They’re familiar with our nurses,” Dr. Tse said. “It is so much better for our patients. It is very exciting.”

Treatment has produced 90% remission of ALL

ALL is the most common pediatric malignancy, accounting for 19% of cancers occurring before age 19. Traditional treatments work well for 90% of ALL patients. For those who relapsed or didn’t respond to chemotherapy, the survival rate was about 10% before CAR-T.

Norton Children’s will be using the Novartis CAR-T product Kymriah, which has FDA approval for use in patients up to 25 years old. CAR-T has produced remission in up to 90% of pediatric ALL patients.

Kymriah is made using the patient’s own white blood cells. CAR-T patients are taken to the Norton Children’s Infusion Center where native T cells are removed from the blood through leukapheresis. These cells are shipped to Novartis, where they are reengineered to express a CAR-T protein that targets the CD19 antigen on leukemia cells. The CAR-T cells are sent back and infused into the child. After the infusion, the CAR-T cells will seek out CD19-positive leukemia cells and destroy them.

“It is like a magic bullet, a homing device to allow the T cells to find the leukemia cells,” Dr. Tse said.

Advanced training needed prior to approval to use therapy

Because the side effects of Kymriah can be serious or even life-threatening, providers at Norton Children’s Cancer Institute underwent extensive training before receiving approval from Novartis to administer Kymriah.

CAR-T treatment can provoke cytokine release syndrome, causing symptoms including fever, respiratory distress and a dangerous drop in blood pressure. Another potential side effect is neurotoxicity, which can result in confusion, delirium, an inability to talk, seizures and coma.

According to Jennifer Thomas, DNP, R.N., director of patient care services for pediatric hematology and oncology and transplant services, months of preparations have preceded CAR-T therapy at Norton Children’s Cancer Institute. Oncology physicians, nurses, pediatric intensive care physicians and nurses, and emergency department physicians and nursing staff all have received special training in how to recognize and treat CAR-T severe side effects.

“It takes a whole care team to prepare for bringing this therapy to the hospital,” Jennifer said.

According to Dr. Tse, he expects more immunotherapy treatments will be available at Norton Children’s Cancer Institute.

“We hope there will be more treatments like this coming along so we can deal with more difficult diseases in the future,” he said.