Libertini, Silvana, Ulrich, Peter, Menssen, Hans, Maier, Harald and Gao, Jingbo (2024) Aggressive Lymphoma after CD19 CAR T-Cell Therapy. The New England journal of medicine, 391 (13). pp. 1217-1226. ISSN 1533-4406

Abstract

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic DNMT3A and TET2 mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant. The PTCL harbored an additional somatic TET2 mutation, which was already detectable in the CAR T-cell apheresis product and the final CAR T-cell product at very low frequencies, providing evidence that clonal hematopoiesis had contributed to lymphomagenesis.

Item Type:	Article
Keywords:	Humans Antigens, CD19 Immunotherapy, Adoptive Lymphoma, T-Cell, Peripheral Receptors, Antigen, T-Cell Receptors, Chimeric Antigen Male Mutation Middle Aged Clonal Hematopoiesis Central Nervous System Neoplasms
Date Deposited:	14 Dec 2024 00:45
Last Modified:	14 Dec 2024 00:45
URI:	https://oak.novartis.com/id/eprint/53231