Personalized cellular therapy achieves complete remission in 90 percent of acute lymphoblastic leukemia patients studied

PUBLIC RELEASE DATE:

15-Oct-2014

Holly Auer Penn Medicine 215-349-5659 215-200-2313 holly.auer@uphs.upenn.edu

Rachel Salis-Silverman Children's Hospital of Philadelphia 267-426-6063 267-970-3685 Salis@email.chop.edu

PHILADELPHIA Ninety percent of children and adults with acute lymphoblastic leukemia (ALL) who had relapsed multiple times or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy, CTL019, developed at the Perelman School of Medicine at the University of Pennsylvania. The results are published this week in The New England Journal of Medicine.

The new data, which builds on preliminary findings presented at the American Society of Hematology's annual meeting in December 2013, include results from the first 25 children and young adults (ages 5 to 22) treated at the Children's Hospital of Philadelphia and first five adults (ages 26 to 60) treated at the Hospital of the University of Pennsylvania. Twenty-seven of the 30 patients in the studies achieved a complete remission after receiving an infusion of these engineered "hunter" cells, and 78 percent of the patients were alive six months after treatment.

"The patients who participated in these trials had relapsed as many as four times, including 60 percent whose cancers came back even after stem cell transplants. Their cancers were so aggressive they had no treatment options left," said the study's senior author, Stephan Grupp, MD, PhD, a professor of Pediatrics in Penn's Perelman School of Medicine and director of Translational Research in the Center for Childhood Cancer Research at the Children's Hospital of Philadelphia. "The durable responses we have observed with CTL019 therapy are unprecedented."

Shannon Maude, MD, PhD, an assistant professor of Pediatrics and a pediatric oncologist at CHOP, and Noelle Frey, MD, MSCE, an assistant professor of Medicine and an oncologist at Penn's Abramson's Cancer Center, are co-first authors of the new study. The research team is led by Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center, along with David Porter, MD, the Jodi Fisher Horowitz Professor in Leukemia Care Excellence and director of Blood and Marrow Transplantation in the Abramson Cancer Center.

CTL019 manufacturing begins with a patient's own T cells, which are collected via an apheresis process similar to blood donation, then reprogrammed in Penn's Clinical Cell and Vaccine Production Facility with a gene transfer technique that teaches the T cells to target and kill tumor cells. The engineered cells contain an antibody-like protein known as a chimeric antigen receptor (CAR), which is designed to bind to a protein called CD19 found on the surface of B cells, including the cancerous B cells that characterize several types of leukemia. The modified "hunter" cells are then infused back into the patient's body, where they both multiply and attack the cancer cells. A signaling domain built into the CAR promotes rapid multiplication of the "hunter" cells, building an army of tumor-killing cells that tests reveal can grow to more than 10,000 new cells for each single engineered cell patients receive.

Nineteen patients in the study remain in remission, 15 with this therapy alone, including a 9 year old who was the first ALL patient to receive the therapy more than two years ago. The follow-up periods reported in the study are more than six months for most patients, with a range from 1.4 to 24 months. Five patients went off-study for alternate therapy, three of whom proceeded to allogeneic stem cell transplants while in remission. Seven patients relapsed, between 6 weeks and 8.5 months after their infusions, including three whose cancers returned as CD19-negative leukemia that would not have been targeted by the modified cells.

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Personalized cellular therapy achieves complete remission in 90 percent of acute lymphoblastic leukemia patients studied