Preventing Toxic Side Effects From CAR-T Cancer Treatments

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The oncology community is excited over the recent approval of Kymriah, which is Novartis’ CAR-T treatment for patients with lymphoma, worried about side effects remain. A number of patients in clinical trials of Novarits’ product and others have developed a hazardous immune reaction called cytokine release syndrome, while others have agonized neurotoxicity. The side effects have the potential to be life threatening.

Currently, scientists at Fred Hutchinson Cancer Research Center stated they’ve found biomarkers connected with cytokine release syndrome and neurotoxicity, and they’ve created algorithms that they think it can be used to detect when the effects are likely to be life-threatening. Their discoveries were published in the journal Cancer Discovery.

To identify the biomarkers, the research team closely monitored 133 patients involved in a trial of a CAR-T that was developed at Fred Hutch to treat chronic lymphocytic leukemia, non-Hodgkin lymphoma or acute lymphoblastic leukemia. They timed the beginning of symptoms and the directions to resolution, leading detailed pathology testing and imaging. Majority of patients developed cytokine release syndrome, which resolved on its own, though 10 suffered serious symptoms, according to a report.

The researchers found two key standards for forecasting severe cytokine release syndrome: a fever of at least 102 and high levels of a specific immune cytokine named MCP-1. Patients who also saw high levels of the cytokine IL-6 faced an increased risk of neurotoxicity, the researchers said. They feel cytokine release syndrome is the forerunner for most cases of neurotoxicity, though more research would be needed to choose the link between the two, they reported.

The study was partially funded by Juno Therapeutics, which dropped to third place in the CAR-T race behind Novartis and Kite after a number of deaths in 2016 in a trial for what was previously the lead candidate, JCAR015. The deaths were contributed to severe swelling in the brain, or cerebral edema. Juno took out the CAR-T from its pipeline in March of 2017.

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