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Guidelines Designed for CAR T-Cell Cancer Therapies

MD Anderson campus

Aerial photograph of MD Anderson campus in 2011 (

20 September 2017. Cancer specialists and scientists at several cancer care centers propose safety guidelines for patients receiving engineered immune cell treatments that often have severe adverse effects. The team led by researchers at MD Anderson Cancer Center in Houston, part of the University of Texas system, published its guidelines in yesterday’s issue of Nature Reviews Clinical Oncology (paid subscription required).

The researchers led by Elizabeth Shpall, director of MD Anderson’s cell therapy laboratory, and Sattva Neelapu, professor of lymphoma and myeloma, aim to provide guidance for emerging treatments using T-cells, white blood  cells from the patient’s immune system, genetically engineered to express chimeric antigen receptor proteins. The therapies reprogram the T-cells with genetic engineering to find and kill cancer cells like an antibody. These modified chimeric antigen receptor or CAR T-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 blood-related cancers.

CAR T-cells are being tested in clinical trials among patients who do respond to conventional treatments for a number of blood-related cancers, which report remission rates as high as 90 percent. In August 2017, FDA approved the first CAR T-cell treatments in the U.S. for patients with a form of stubborn or relapsing acute lymphoblastic leukemia. But along with the successes come high rates of severe adverse effects, leading in some cases to patient deaths. As reported in Science & Enterprise earlier this month, FDA put a clinical hold on two trials testing CAR T-cells when a patient died in one of the trials.

The guidelines proposed by the MD Anderson researchers — with colleagues from the Mayo Clinic, Moffitt Cancer Center in Tampa, and Sylvester Cancer Center at the University of Miami — address two of the main adverse reactions experienced by CAR T-cell patients. Cytokine-release syndrome is a set of reactions to immunotherapies with symptoms often resembling the flu, such as fever, nausea, chills, and muscle aches. In severe cases, however, cytokine-release syndrome can pose an emergency for patients and lead to life-threatening complications.

Another adverse reaction, but less common, is neurological toxicity called CAR-T-cell-related encephalopathy syndrome that in some cases can lead to lethal swelling in the brain. Both of the adverse reactions are treatable, however, and the guidelines offer recommendations for pre-treatment preparations, monitoring, identification of emerging adverse reactions, and treatment recommendations based on the severity of the patient’s condition.

The guidelines are a product of the CAR-T-cell-therapy-associated toxicity, or Cartox, Working Group, made up of professionals from a number of institutions with experience treating cancer patients with CAR T-cells. The group’s recommendations cover diagnostics and treatments for adverse reactions to these treatments. In cases of neurological toxicity, for example, the guidelines recommend a simple question-and-answer test, writing a standard sentence, and counting backwards from 100 by tens. Other recommendations offer ways of controlling expression of the protein interleukin-6, considered a driver of cytokine-release syndrome.

“While we all work on those issues, and learn how to better manage and harness these therapies,” says Shpall in an MD Anderson statement, “the Cartox algorithms provide ground rules for patient safety.”

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