“Cases have been reported up to several years after administration.”
The risk was indicated by health authorities as soon as these drugs were placed on the market, but patients are not necessarily informed of this. And this risk was less than the benefits, hence the validation of their marketing. But today, faced with new studies, the Pharmacovigilance Committee (PRAC) of the European Medicines Agency (EMA) “alerts health professionals about the risk of secondary cancers linked to T cells with gene therapy drugs called “CAR-T cells”” reports theMedicines Agency in France (ANSM), June 26. We speak of “secondary cancer” when a patient suffering from cancer (present or past) develops a second cancer different from the first cancer.
CAR-T cells are the basis of a new approach to cancer treatment based on immunotherapy, i.e. stimulating the patient’s immune system against cancer cells. In concrete terms, white blood cells (T cells) from the patient are collected, genetically modified to target cancer cells and then reinjected into the patient. The first drugs of this type were authorized in France in 2018 for the treatment of blood cancers (e.g. leukemia) and lymphomas. If the PRAC is sounding the alarm today, it is after evaluating the data relating to 38 cases of secondary cancers linked to T cells, reported on approximately 42,500 patients treated with CAR-T cells.
“Patients must be monitored”
Biological samples were tested in half of the cases, revealing the presence of the genetic construct of CAR-T cells in 7 cases. This suggests, for these latter cases, that CAR-T cells may have played a role in the development of these secondary cancers.
“Cases have been reported within weeks and up to several years after administration of CAR-T cells” specifies the ANSM. A study published in June 2024 in the New England Journal of Medicine and conducted on 724 patients who had received T-cell therapies concluded that the risk of a second tumor was “rare”. However, according to the ANSM “Patients treated with these drugs should be monitored throughout their lives for the possible presence of second cancers. In France, the medicines concerned are:
- Abecma (idecabtagene vicleucel);
- Breyanzi (lisocabtagene maraleucel);
- Carvykti (ciltacabtagene autoleucel), ceased marketing in France since March 29, 2023;
- Kymriah (tisagenlecleucel);
- Tecartus (brexucabtagene autoleucel);
- Yescarta (axicabtagene ciloleucel).
Europe is not the only one to consider the possible risk linked to these drugs. In the United States, the American Medicines Agency (FDA) opened an investigation in November 2023 “on a serious risk” of second cancer after T lymphocyte immunotherapy.