Joining us today are Terry Fry, MD and Mike Verneris, MD to explore cellular therapy for the treatment of pediatric cancers.

Dr. Fry is the Robert and Kathleen Clark Endowed Chair in Pediatric Cancer Therapeutics and Dr. Verneris is the Barton Family Endowed Chair of Bone Marrow Transplant at Children's Colorado.

In this episode:

• A new immunotherapy known as cellular therapy, or specifically the chimeric antigen receptor T cell therapy (CAR-T cell), is bringing hope to pediatric patients with blood cancers.
• Two breakthrough events in the field of immunotherapy made CART-T cell therapy possible:
  • Checkpoint inhibitors: a concept where agents can "take the brakes" off the immune, unleashing a sort of preexisting immune response against the tumor
  • Adult epithelia cancers
• For cancers like pediatric tumors, mutations aren't present or aren't present at high enough levels for checkpoint inhibitors to work.
• CAR-T cell therapy is different from checkpoint inhibitors in that the immune system, the T cells, are taken and essentially educated in a different way. The T cells are redirected so they can see the tumors that they weren't naturally developed to see.
• The FDA labor indication is refractory leukemia at the time of diagnosis, relapse or second relapse.
• There is a 70 to 90% complete remission induction rate in phase one CAR-T therapy clinical trials in patients who had estimated durations of survival of only weeks to months.
• The CAR-T cell approach may be considered an alternative to chemotherapy.
• Side effects of CAR-T cell therapy include:
  • Patients become neutropenic, have low counts and are at risk for bacterial infection (because chemotherapy is given before cells are infused)
  • Cytokine release syndrome
  • Transient neurotoxicity, ranging from subtle neurologic changes to severe side effects like seizures or even coma
• Because of leukemic resistance, half of patients that go into remission will relapse by year, in spite of a successful CAR-T cell treatment upfront.
• The pros and cons of a bone marrow transplant (BMT) versus CAR-T cell therapy are:
  • BMT patients get mild oblation, likely face sterility, late complications, secondary malignancies and more. With CAR-T cells, patients get a single infusion and risk about a month of significant toxicity, but side effects are mitigated after that. The only long-term side effect is potentially a lack of b-cells.