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Personalized Leukemia Immunotherapy Gets 90 Pct Remission


T-cell (NIAID/NIH)

16 October 2014. Nine in 10 children and adults in early-stage clinical trials of a personalized therapy harnessing the patients’ immune systems achieved full remission of their acute lymphoblastic leukemia. The findings of the team from University of Pennsylvania and Children’s Hospital of Philadelphia are reported today in New England Journal of Medicine (paid subscription required).

The trials tested a personalized therapy code-named CTL019 with 30 patients having relapsed or unresponsive cases of acute lymphoblastic leukemia, a cancer of blood and bone marrow. The disease progresses quickly, making an overabundance of immature lymphocytes, a type of white blood cell. It is also the most common type of cancer among children, although it can also affect adults.

The process to make CTL019 starts with an individual’s blood cells and separates out T cells, white blood cells used by the immune system to fight invading pathogens, then reprograms the T cells with genetic engineering to find and kill cancer cells. The engineered T cells then become hunter cells, containing a protein known as chimeric antigen receptor that acts like an antibody. These hunter cells are infused back into the patient, seeking out and binding to a protein called CD19 found on the surface of B cells — another type of white blood cell — associated with several types of leukemia.

Among the properties programmed into CTL019 is the ability of hunter cells to quickly multiply and accumulate to battle the cancerous cells. The authors, led by pediatrics professor Stephan Grupp of Children’s Hospital, say their tests show some 10,000 hunter cells are produced for each engineered T cell received by patients.

The trials enrolled 25 patients, ages 5 to 22, at Children’s Hospital and 5 adult patients, ages 26 to 60, at University of Pennsylvania. “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,” says Grupp in a hospital statement. “Their cancers were so aggressive they had no treatment options left.”

The researchers began giving the CTL019 infusions two years ago. Of the 30 patients receiving these personalized infusions, 27 or 90 percent, achieved complete remission. Some 78 percent of the patients survived at least 6 months after the treatments. Of the original patients, 19 remain in remission, 15 of whom received only the CTL019 therapy, while 5 others sought out other therapies, including stem cell transplants. Also of the original patients, 7 relapsed between 6 weeks and 8.5 months after the infusions, although 3 of the relapsed patients developed a different form of leukemia, one where the CD19 protein is not expressed, thus it would not have been helped by the CTL019 therapy.

All of the patients receiving CTL019 experienced an adverse reaction a few days after the infusions called a cytokine release syndrome. While these reactions cause flu-like symptoms, they’re considered an indicator of hunter cells’ progress in fighting the cancer cells. However, nine patients developed severe cytokine release syndrome reactions requiring treatment with immunosuppressant drugs and steroids. All of the patients fully recovered from these reactions.

The pharmaceutical company Novartis is licensing the immunotherapy technology, under an agreement reached two years ago with University of Pennsylvania. In July 2014, CTL019 received breakthrough therapy status from the U.S. Food and Drug Administration, which provides expedited review for new therapies treating serious conditions and where the treatments are shown to be an improvement over current methods.

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