The promising treatment has come under scrutiny following reports of deaths, hospitalisations, and serious illness.
The FDA is investigating CAR T therapy after reports of malignancies, including CAR-positive lymphoma, following treatment with “several products in the class”.
“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, FDA is investigating the identified risk of T cell malignancy with serious outcomes, including hospitalization and death, and is evaluating the need for regulatory action,” the statement says.
The FDA has not specified which products have been reported, but says “the risk of T-cell malignancies is applicable to all currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T cell immunotherapies.”
In the US these are: idecabtagene vicleucel (Abecma), lisocabtagene maraleucel (Breyanzi), ciltacabtagene autoleucel (Carvykti), tisagenlecleucel (Kymriah), brexucabtagene autoleucel (Tecartus) and axicabtagene ciloleucel (Yescarta).
The TGA told OR it was aware of the FDA investigation into BCMA-directed and CD-19 directed genetically modified autologous CAR T therapies, noting four autologous CAR T cell therapies are approved for use in Australia:
- ciltacabtagene autoleucel (Carvykti, Janssen-Cilag), for relapsed or refractory multiple myeloma;
- tisagenlecleucel (Kymriah, Novartis Pharmaceuticals Australia) for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and for children and adults up to 25 years of age with B-cell precursor acute lymphoblastic leukaemia (ALL);
- brexucabtagene autoleucel (Tecartus, Gilead Sciences) for relapsed or refractory mantle cell lymphoma (MCL) and for B-cell acute lymphoblastic leukaemia (B-ALL); and
- axicabtagene ciloleucel (Yescarta, Gilead Sciences) for relapsed or refractory large B-cell lymphoma (LBCL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
“The Product Information (PI) for all four include warnings that patients receiving these therapies may develop secondary malignancies and should be monitored for at least 15 years post infusion.
“These are not confirmed safety issues at this time and the TGA is closely monitoring evidence in this space. This includes reviewing adverse event reports and medical literature, and liaison with international regulators for the four CAR-T immunotherapies that are registered on the Australian Register of Therapeutic Goods. If a safety issue is confirmed, then the TGA will take prompt regulatory action as appropriate,” the authority said.
“We also note that the FDA has stated the overall benefits of these products continue to outweigh their potential risks for their approved uses. The TGA will continue to monitor the FDA’s investigation and any resultant regulatory action.”
The FDA data on adverse events, available on its public dashboard, shows 7,205 reports reports received for the four products that are also approved in Australia, between 2017 and 2023 (although the FDA points out the events are not necessarily caused by the drugs). Of these, 6,665 were characterised as serious. The largest number of reports were for cytokine release syndrome, neurotoxicity and pyrexia.
