Aggressive Lymphoma after CD19 CAR T-Cell Therapy
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 <i>DNMT3A</i> and <i>TET2</i> 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 <i>TET2</i> 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.
Authors
- Daniel Hübschmann (ORCID: https://orcid.org/0000-0002-6041-7049)
- Paul Jäger (ORCID: https://orcid.org/0000-0001-9250-2064)
- Ingram Iaccarino (ORCID: https://orcid.org/0000-0001-7324-993X)
- Raphael Koch (ORCID: https://orcid.org/0000-0002-5581-5122)
- Kathrin Nachtkamp (ORCID: https://orcid.org/0000-0001-5893-2298)
- Jutta M. Rox
- Peter‐Martin Bruch (ORCID: https://orcid.org/0000-0002-9992-3109)
- Donnacha Fitzgerald (ORCID: https://orcid.org/0000-0003-4927-7484)
- Silvana Libertini (ORCID: https://orcid.org/0000-0003-2633-1564)
- Schayan Yousefian (ORCID: https://orcid.org/0000-0003-0902-0369)
- Simon Haas (ORCID: https://orcid.org/0000-0001-9227-2051)
- Jörg H. W. Distler (ORCID: https://orcid.org/0000-0001-7408-9333)
- Sven Guenther Meuth (ORCID: https://orcid.org/0000-0003-2571-3501)
- Aleksandar Radujkovic (ORCID: https://orcid.org/0000-0002-8543-5016)
- Heiko Trautmann (ORCID: https://orcid.org/0000-0002-9000-4747)
- Nora Liebers
- Frédérik Damm (ORCID: https://orcid.org/0000-0001-5553-1173)
- Nagarajan Paramasivam (ORCID: https://orcid.org/0000-0002-7126-8472)
- Laura Wiegand (ORCID: https://orcid.org/0000-0002-9917-7396)
- Gerald Antoch (ORCID: https://orcid.org/0000-0001-7834-3714)
- Sascha Dietrich (ORCID: https://orcid.org/0000-0002-0648-1832)
- Ulrich Germing
- Iréne Esposito (ORCID: https://orcid.org/0000-0002-0554-2402)
- Harald J. Maier
- Malte Jacobsen (ORCID: https://orcid.org/0000-0003-0780-0003)
- Monika Brüggemann (ORCID: https://orcid.org/0000-0001-5514-5010)
- Junyan Lu (ORCID: https://orcid.org/0000-0002-9211-0746)
- Ron‐Patrick Cadeddu (ORCID: https://orcid.org/0000-0003-0484-5660)
- Johannes Fischer (ORCID: https://orcid.org/0000-0002-2079-1845)
- Marc Seifert (ORCID: https://orcid.org/0000-0001-9453-369X)
- Hans D. Menssen (ORCID: https://orcid.org/0000-0002-1895-4713)
- Thomas Ulrych
- Christina Schniederjohann (ORCID: https://orcid.org/0009-0001-2693-8086)
- Jingbo Gao
- Frederik Lars Giesel (ORCID: https://orcid.org/0000-0002-9669-5593)
- Peter Ulrich (ORCID: https://orcid.org/0000-0001-6672-2223)
- Guido Kobbe
- Ben‐Niklas Baermann (ORCID: https://orcid.org/0009-0000-1699-9478)
- Maximilian Seidel
Institutions
- Düsseldorf University Hospital (DE)
- Research Institute of Radiology (BY)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- New England Journal of Medicine
- Published
- 2024-10-02
- DOI
- https://doi.org/10.1056/nejmoa2402730
- Citations
- 34
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 9.61
Funders
- Hairy Cell Leukemia Foundation
- Deutsche Forschungsgemeinschaft
- Else Kröner-Fresenius-Stiftung
- Deutsche Krebshilfe