T cell malignancies after CAR T cell therapy in the DESCAR-T registry

Abstract

The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.8%) received axicabtagene ciloleucel, 205 (6.7%) brexucabtagene autoleucel, 44 (1.4%) lisocabtagene maraleucel and 769 (25.1%) tisagenlecleucel. All multiple myeloma patients received idecabtagene vicleucel, with none receiving ciltacabtagene autoleucel. After a median follow-up of 12.7 months for B cell lymphoma, 17.7 months for B cell ALL and 6.3 months for multiple myeloma, only one (0.03%) patient developed a T cell malignancy after CAR T infusion. Specifically, the patient was diagnosed with a primary cutaneous CD30⁺ T cell lymphoproliferative disorder (anaplastic lymphoma kinase-negative) 3 years after receiving tisagenlecleucel therapy for diffuse large B cell lymphoma. This was associated with the integration of a CAR clone into the tumor suppressor gene PLAAT4 (phospholipase A and acyltransferase 4). Thus, the development of this secondary T cell malignancy might be linked to the use of CAR T cell therapy. In conclusion, our findings indicate a very low risk of T cell malignancy after CAR T cell therapy.