Aggressive Lymphoma after CD19 CAR T-Cell Therapy

作者：Guido Kobbe, Monika Brüggemann, Ben‐Niklas Baermann, Laura Wiegand, Heiko Trautmann, Schayan Yousefian, Silvana Libertini, Hans D. Menssen, Harald J. Maier, Peter Ulrich, Jingbo Gao, Peter‐Martin Bruch, Nora Liebers, Aleksandar Radujkovic, Marc Seifert, Christina Schniederjohann, Nagarajan Paramasivam, Donnacha Fitzgerald, Maximilian Seidel, Iréne Esposito, Ulrich Germing, Ron‐Patrick Cadeddu, Kathrin Nachtkamp, Paul Jäger, Thomas Ulrych, Johannes Fischer, Jutta M. Rox, Frederik L. Giesel, Raphael Koch, Gerald Antoch, Jörg H. W. Distler, Sven G. Meuth, Malte Jacobsen, Daniel Hübschmann, Junyan Lu, Ingram Iaccarino, Simon Haas, Frédérik Damm, Sascha Dietrich · 发表于：New England Journal of Medicine · 年份：2024 · DOI：10.1056/nejmoa2402730 · 被引用次数：49 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Immune Cell Function and Interaction

Summary 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.