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Fred Hutch researcher Dr. Cameron Turtle led the study. (Fred Hutch Photo)

CAR T immunotherapies — which genetically program immune cells to fight cancer — hold incredible promise for cancer patients who have run out of other options.

But the treatments also have severe and sometimes deadly side effects.

A new study from Seattle’s Fred Hutchinson Cancer Research Center might point the way to overcoming those negative effects by using an algorithm that can predict which patients will react most extremely

The study, which was based on a clinical trial of 133 patients, is the largest to date on the side effects of CAR T immunotherapy. It was published early Thursday in the journal Cancer Discovery.

“It’s essential that we understand the potential side effects of CAR T therapies,” Fred Hutch researcher Dr. Cameron Turtle said in a press release. “While use of these cell therapies is likely to dramatically increase because they’ve been so effective in patients with resistant or refractory B-cell malignancies, there is still much to learn.”

The study, which was led by Turtle, found biomarkers that could be red flags of cytokine release syndrome and neurotoxicity, the two most extreme side effects of CAR T. They also used that information to create an algorithm that could predict which patients are most likely to have life-threatening symptoms.

These side effects have had a clear impact on the development of CAR T therapies. When five patients in a clinical trial died of neurotoxicity last year, Fred Hutch spin-out Juno Therapeutics was forced to pull its lead CAR T candidate.

The FDA recently approved the first CAR T therapy to come to market, a drug called Kymriah developed by Swiss biopharmaceutical giant Novartis that treats children with advanced leukemia. Eighty-three percent of children treated with the drug in trials went into remission, a staggering number for the kinds of extremely sick patients that took it.

The therapies are currently most effective against blood cancers, including leukemia and lymphoma, and all the patients studied in this trial had a form of advanced blood cancer that had resisted traditional therapies

Of the 133 patients studied, 93 experienced cytokine release syndrome, although only ten experienced the most severe symptoms. Fifty-three patients experienced neurotoxicity, of which seven had life-threatening symptoms. Overall, five percent of patients experienced life-threatening side effects.

But for those who could overcome or avoid side effects, the outlook is good. In previous studies, a high percentage of patients with advanced, deadly blood cancers have gone into complete remission after being treated with CAR T immunotherapies, sometimes as high as 90 percent.

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