CAR-T cell therapy under investigation by FDA

The promising treatment has come under scrutiny following reports of deaths, hospitalisations and serious illness.

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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 hospitalisation 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.”

Bruce articulates what many of us are asking right now. And echoes the surprise of today’s announcement! #immunotherapy https://t.co/jPsYrYppDz

— Krishna Komanduri, MD, FASTCT (@drkomanduri) November 28, 2023

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 The Medical Republic 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 were 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,” the authority said.

“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.

“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.”