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<p>Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we present a case of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) that developed eight months following CD19-directed CAR T cell therapy (lisocabtagene maraleucel) in a 66-year-old male patient with recurrent diffuse large B cell lymphoma. The patient initially achieved complete remission but later developed a subcutaneous mass and systemic lymphadenopathy. Histopathology and flow cytometry confirmed a diagnosis of PTCL-NOS with a CD3 + , CD8 + , and CD30 + phenotype, as well as clonal T cell receptor gene rearrangements. No immunoglobulin rearrangements were detected, ruling out a lineage switch. Furthermore, the CAR transgene was undetectable by RNA-in situ hybridization, and flow cytometry showed no CAR protein expression, suggesting that the lymphoma was not caused by CAR gene integration. This case highlights the importance of re-biopsy in cases of suspected relapse following CAR T cell therapy, and emphasizes the need for long-term monitoring. While a direct causal link remains unclear, industry–academia collaboration is crucial for investigating the mechanisms underlying secondary T cell malignancies and improving the safety of CAR T cell therapy.</p>

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Peripheral T cell lymphoma following CD19-targeted chimeric antigen receptor T cell therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Hiro Tatetsu,
  • Koji Kato,
  • Atsushi Wada,
  • Taichi Hirano,
  • Shikiko Ueno,
  • Yuko Miyasato,
  • Asami Yamada,
  • Takafumi Shichijo,
  • Yusuke Higuchi,
  • Yujiro Ueda,
  • Kisato Nosaka,
  • Yoshiki Mikami,
  • Kennosuke Karube,
  • Masao Matsuoka,
  • Jun-ichirou Yasunaga

摘要

Chimeric antigen receptor (CAR) T cell therapy has significantly improved outcomes for patients with refractory B cell lymphoma. However, rare cases of secondary T cell lymphomas have raised safety concerns. Here, we present a case of peripheral T cell lymphoma not otherwise specified (PTCL-NOS) that developed eight months following CD19-directed CAR T cell therapy (lisocabtagene maraleucel) in a 66-year-old male patient with recurrent diffuse large B cell lymphoma. The patient initially achieved complete remission but later developed a subcutaneous mass and systemic lymphadenopathy. Histopathology and flow cytometry confirmed a diagnosis of PTCL-NOS with a CD3 + , CD8 + , and CD30 + phenotype, as well as clonal T cell receptor gene rearrangements. No immunoglobulin rearrangements were detected, ruling out a lineage switch. Furthermore, the CAR transgene was undetectable by RNA-in situ hybridization, and flow cytometry showed no CAR protein expression, suggesting that the lymphoma was not caused by CAR gene integration. This case highlights the importance of re-biopsy in cases of suspected relapse following CAR T cell therapy, and emphasizes the need for long-term monitoring. While a direct causal link remains unclear, industry–academia collaboration is crucial for investigating the mechanisms underlying secondary T cell malignancies and improving the safety of CAR T cell therapy.