Remission was achieved in 90% of children and adults with acute lymphoblastic leukemia (ALL) who had relapsed multiple times or failed to respond to standard therapies after receiving CTL019, an investigational personalized cellular therapy. These results were published in the New England Journal of Medicine (2014;371:1507-1517).

The new data include results from the first 25 children and young adults (age 5 to 22 years) treated at the Children’s Hospital of Philadelphia and first five adults (age 26 to 60 years) treated at the Hospital of the University of Pennsylvania. A complete remission was achieved by 27 of the 30 patients in the studies after they received an infusion of these engineered “hunter” cells, and 78% of the patients were alive 6 months after treatment.

“The patients who participated in these trials had relapsed as many as four times, including 60% 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.”

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CTL019 manufacturing begins with a patient’s own T cells, which are collected via an apheresis process similar to blood donation, then reprogrammed 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 2 years ago.

All patients who received the CTL019 hunter cells experienced a cytokine release syndrome (CRS) within a few days after receiving their infusions, which is a key indicator that the engineered cells have begun proliferating and killing tumor cells in the body. During this time, 22 of 30 patients experienced mild to moderate CRS and eight patients developed severe CRS.

“Our results support that CTL019 can produce long-lasting remissions for certain heavily pre-treated ALL patients without further therapy,” Frey said. “For our patients who have already relapsed after stem cell transplants, or don’t have any options for donors, this option has provided new hope.”

In July 2014, the US Food and Drug Administration granted CTL019 its Breakthrough Therapy designation for the treatment of relapsed and refractory adult and pediatric ALL, a step which is intended to expedite the development and review of new medicines that treat serious or life-threatening conditions, if a therapy has demonstrated substantial advantages over available treatments.