The FDA warns of the risk of a type of tumors in patients treated with CAR-T cells

2023-11-29 17:48:17

The United States Food and Drug Administration The FDA has issued a statement saying it has received reports of T-cell tumors in patients receiving various CAR-T cell treatments. As quoted in the statement, “although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA is investigating the identified risk of T-cell neoplasia with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action.

According to the statement, “although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA is investigating the identified risk of T cell neoplasia with severe outcomesincluding hospitalization and death, and is evaluating the need for regulatory action.

In statements to Science Media CentreIgnacio Melero, from the University of Navarra, researcher of the CIMA and co-director of the Department of Immunology and Immunotherapy at the Clínica Universidad de Navarraclarifies that “this is an adverse effect that we feared would be observed in very long series of patients. “It occurs with low frequency, and in the treatment of diseases for which CAR-Ts are indicated, the benefit far outweighs the risk.”

The FDA recommends that patients and clinical trial participants receiving treatment with these products should be monitored for life for new malignancies. Should a new malignancy occur after treatment with these products, contact the manufacturer to report the event and obtain instructions on collecting patient samples to test for the presence of the chimeric antigen receptor (CAR) transgene.

Melero comments that «The reason for this adverse effect lies in the enormous number of cell divisions that the CAR lymphocytes undergo once they are infused back into the patient and that to generate the CAR [receptor de antígeno quimérico] The integration of DNA into the patient’s lymphocytes is necessary. The integrations in the DNA of the nucleus of these lymphocytes occur practically at random, in such a way that insertions can occur that act by deregulating oncogenes (insertional mutagenesis). “A strategy in clinical research consists of including pharmacological targets in the genetic material to form the CAR to selectively eliminate lymphoma that could form from CAR-T cells (the so-called suicide genes).”

In any case, he concludes, “the risk-benefit balance in the currently approved indications for CAR-T therapies is immensely favorable.”