In a landmark decision for the field of cancer immunotherapy, the U.S. Food and Drug Administration (FDA) approved a personalized cellular therapy developed by the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) for the treatment of patients up to 25 years of age with B–cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. The approval was granted to Novartis for the chimeric antigen receptor (CAR) T–cell therapy, Kymriah™ (tisagenlecleucel, formerly CTL019).

In 2012, Penn and Novartis entered into a global collaboration to further research, develop and commercialize Kymriah and other CAR–T cell therapies for the treatment of cancers. Kymriah is the first therapy based on gene transfer approved by the FDA.

“This is a turning point in the fight against B–cell ALL that opens up opportunities for patients across the world who desperately need new options,” said Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in Penn’s Perelman School of Medicine and director of the Center for Cellular Immunotherapies in the Abramson Cancer Center.

Kymriah is expected to be available through a network of certified treatment centers throughout the United States. "We delivered engineered T–cell therapy at CHOP for the first pediatric patient in the world, Emily Whitehead, who was only six years old when her leukemia stopped responding to conventional treatments. Emily’s cancer remains in remission, and in larger trials, we’re seeing overall remission rates over 80 percent, which is a remarkable improvement upon previous treatment success rates,” said lead investigator of the CHOP and global trials of the therapy, Stephan Grupp, MD, PhD, the Yetta Deitch Novotny Professor of Pediatrics at Penn and director of the Cancer Immunotherapy Frontier Program and chief of the section of Cell Therapy and Transplant at CHOP.

The new treatment modifies patients’ own immune T cells, which are collected and reprogrammed at the Novartis manufacturing facility to potentially seek and destroy the patients’ leukemia cells. After being infused back into patients’ bodies, these newly built “hunter” cells both multiply and attack, targeting cells that express a protein called CD19. Tests reveal that the army of hunter cells can grow to more than 10,000 new cells for each single engineered cell patients receive, producing high remission rates in completely refractory leukemia – and can survive in the body for years.

CTL019 was first tested at Penn in 2010, in adult patients with advanced chronic lymphocytic leukemia (CLL). In 2012, CHOP became the first institution to investigate Kymriah in pediatric patients with ALL, the most common childhood cancer. About 20 percent of the 3,500 pediatric and young adult patients diagnosed every year with ALL in the United States relapse or do not respond to conventional treatment. Those early–stage clinical trials, in which more than 90 percent of patients achieved a complete remission one month after receiving the therapy, led to a global registration trial in 2015, involving 68 children and young adults with advanced ALL treated at 25 centers across the world. Eighty–three percent of the patients who received a single dose of their own engineered cells achieved a complete remission.

Many patients in the ALL trials experienced a side effect called cytokine release syndrome (CRS) including grade 3 or grade 4. Patients were treated with the immunosuppressant drug tocilizumab or short courses of steroids to combat the symptoms.