Aggressive Lymphoma after CD19 CAR T-Cell Therapy

N Engl J Med. 2024 Oct 3;391(13):1217-1226. doi: 10.1056/NEJMoa2402730.

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.

Publication types

  • Case Reports

MeSH terms

  • Antigens, CD19*
  • Central Nervous System Neoplasms / immunology
  • Central Nervous System Neoplasms / therapy
  • Clonal Hematopoiesis
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Lymphoma, T-Cell, Peripheral* / immunology
  • Lymphoma, T-Cell, Peripheral* / therapy
  • Male
  • Middle Aged
  • Mutation
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / therapeutic use
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / therapeutic use

Substances

  • Antigens, CD19
  • tisagenlecleucel
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen