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The FDA Oncologic Drugs Advisory Committee (ODAC) unanimously (10-0) recommended approval of tisagenlecleucel, an investigational chimeric antigen receptor T-cell (CAR-T) therapy, for the treatment of relapsed or refractory (r/r) pediatric and young adult patients with B-cell acute lymphoblastic leukemia (ALL).

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ALL comprises approximately 25 percent of cancer diagnoses among children under 15 years old and is the most common childhood cancer in the U.S. Effective treatment options for patients with r/r ALL are limited. In pediatric and young adult patients with B-cell ALL who have relapsed multiple times or become refractory to treatment, the 5-year disease-free survival is less than 10-30 percent.


"For patients with these types of aggressive leukemia (B-ALL) and lymphoma (DLBCL), the advances made in the past year using this immuno-gene (CAR-T) therapy will have more impact than any other in recent decades," Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at the Mount Sinai Icahn School of Medicine, New York City, told Oncology Times. "These terrible cancers generally kill patients within months, but the majority of the CAR-T treated patients go into complete remission and some of them appear to be cured.


"The FDA Advisory Committee's unanimous recommendation to approve the first CAR-T therapy will pave the way for multiple FDA approvals this year and then near-term approvals for other types of lymphoma and myeloma," he continued. "Ongoing trials in common tumor types such as breast cancer and prostate cancer will be guided by the unprecedented success we have seen in leukemia and lymphomas."


The ODAC recommendation is based on the review of the tisagenlecleucel r/r B-cell ALL development program, which includes the ELIANA study (NCT02435849), the first pediatric global CAR-T cell therapy registration trial. Findings from a U.S. multicenter trial and a single-site trial examining the safety and efficacy of tisagenlecleucel among pediatric and young adult patients with r/r B-cell ALL also supported the recommendation and the Biologics License Application.


Tisagenlecleucel was first developed by the University of Pennsylvania (Penn) and uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular responses as well as persistence of tisagenlecleucel after it is infused into the patient, which may be associated with long-lasting remissions in patients. Children's Hospital of Philadelphia (CHOP) was the first institution to investigate tisagenlecleucel in the treatment of pediatric patients and led the single site trial.


"It is encouraging to see the FDA panel's recommendation and continued momentum behind this innovative therapy, which has potential to help young patients with relapsed/refractory B-cell ALL," said the Penn team's leader, Carl June, MD, the Richard W. Vague Professor of Immunotherapy, Director of the Center for Cellular Immunotherapies in Penn's Perelman School of Medicine and Director of the Parker Institute for Cancer Immunotherapy at Penn.


"We know firsthand from treating children and young adults with relapsed/refractory B-cell ALL that they desperately need innovative medicines that provide a new approach to managing this aggressive disease," added Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at the Perelman School of Medicine at Penn, and Director of the Cancer Immunotherapy Frontier Program and Chief of the Section of Cellular Therapy and Transplant at CHOP.