New Cancer Therapy’s Toxic Side Effects Can Be Predicted in Patients

Researchers have discovered ways of determining whether patients receiving a new and advanced cancer treatment, CAR T-cell immunotherapy, may be at an increased risk of suffering from severe, sometimes fatal, toxic side effects.

Less than 2 months ago, the FDA approved the first CD19 CAR T-cell therapy, Kymriah (tisagenlecleucel), for the treatment of acute lymphoblastic leukemia (ALL, an advanced blood cancer) in certain young patients.

Other CD19 CAR T-cell therapies are in development and reports have surfaced that a small number of patients who received this immunotherapy in clinical trials died from severe neurotoxicity. Researchers decided to conduct a thorough examination and find out why this happened.

The research team examined data on 133 patients with severe lymphomas and leukemias who received a CD19 CAR T-cell infusion developed at Fred Hutchinson Cancer Research Center in Seattle.

After about a month, 53 patients (40%) experienced neurologic adverse events, while 4 of the 133 patients (3%) developed fatal neurotoxicity, researchers reported in the journal Cancer Discovery.

Researchers found that patients who experienced neurotoxicity were predominantly younger and had B-cell ALL, higher tumor burden and more CD19-positive cells in their bone marrow compared to those who didn’t have the toxicity. Also, those with severe neurotoxicity had endothelial activation, a condition that can lead to leaking capillaries, blood-clotting abnormalities and disruption of the blood-brain barrier. These effects were seen in patients with severe neurotoxicity.

The research team then developed a predictive algorithm based on certain side effects experienced within the first 36 hours after an infusion. The algorithm identifies patients who face an increased risk for severe neurotoxicity.

Alanna M.

Alanna M. is a graduate of Pace University.

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