The US Food and Drug Administration (FDA) has announced its intention to investigate the safety of CAR-T therapies following reports that they could be linked to the development of T-cell cancers.

Following reports from clinical trials and post-marketing adverse event data sources, the wide probe is directed at patients who received treatment with all currently approved BCMA- or CD19-directed autologous CAR-T cell immunotherapies.

CAR-T-cell therapy is a type of immunotherapy that involves collecting and using patients’ own immune cells to treat conditions including lymphoma, leukaemia and multiple myeloma.

T-cell malignancies have been seen in patients treated with several approved products in the class, including Bristol Myers Squibb’s (BMS) Abecma (idecabtagene vicleucel) and Breyanzi (lisocabtagene maraleucel), Johnson & Johnson and Legend Biotech’s Carvykti (ciltacabtagene autoleucel), Novartis’s Kymriah (tisagenlecleucel), and Gilead and Kite’s Yescarta’s Tecartus (brexucabtagene autoleucel) and Yescarta (axicabtagene ciloleucel).

Currently, the potential risk of developing secondary malignancies is labelled as a class warning in the US prescribing information for approved BCMA-directed and CD19-directed genetically modified autologous T cell immunotherapies, and the overall benefits of these products continue to outweigh their potential risks.

“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 malignancy with serious outcomes, including hospitalisation and death, and is evaluating the need for regulatory action,” said the regulator.

Post-marketing requirements under Section 505(o) of the Federal Food, Drug and Cosmetic Act were included when these products were initially approved to conduct a 15-year long-term follow-up observational study to assess the long-term safety and to evaluate the occurrence of secondary malignancies after treatment.

Companies including Gilead, BMS, Johnson & Johnson and Novartis have all responded to the investigation, expressing their confidence in their products and their overall safety as treatments.

Johnson & Johnson commented: "We have shared our data with the FDA and are working with the agency as they assess this newly identified class-effect safety signal.”

The FDA has recommended that “patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies".

https://www.pmlive.com/pharma_news/fda_to_investigate_risk_of_t-cell_malignancy_from_car-t_cell_immunotherapies_1504347