Study Seeks to Predict Those at Risk for CAR-T Cell Therapy Side Effects

Chimeric Antigen Receptor(CAR)-T cell therapy is an exciting advancement for the treatment of multiple types of blood cancers, but it is not without risk.

CAR-T cell therapy works by removing a patient’s T cells, reengineering them to destroy cancer cells and then infusing them back into the patient’s body, thus improving outcomes for many patients. This process can result in an increased number of cytokines — molecules that mediate and regulate immunity and inflammation — into the blood stream. As a result, patients can experience side effects like fever, increased heart rate, difficulty breathing and low blood pressure.

Researchers at Moffitt Cancer Center recently conducted a study to identify possible risk fac- tors that could help a physician know if patients are more likely to have side effects before they receive CAR-T cell therapy. They analyzed 75 patients with large B-cell lymphoma who were treated with Yescarta (axicabtagene ciloleucel). Patients with an increased level of interleukin

6 (an inflammatory molecule) had higher rates of nervous system damage called neurotoxicity; cytokine release syndrome (a dangerous, inflammatory result of overactive T cells); and death. Also noted was a potential relationship between myeloid cells and regulatory T cells with cytokine release syndrome and neurotoxicity.

“Identifying which CAR-T patients may be more susceptible to those severe toxicities before therapy could allow us to better tailor their care to mediate or reduce those adverse reactions,” said Dr. Marco Davila, study corresponding author, associate member of the Blood and Marrow Transplant and Cellular Immunotherapy Department and medical director of Cell Therapies at Moffitt.

Ultimately, study researchers determined that further research on the side effects of CAR-T cell therapy is needed.