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T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy

  • Guido Ghilardi,
  • Joseph A. Fraietta,
  • James N. Gerson,
  • Vivianna M. Van Deerlin,
  • Jennifer J. D. Morrissette,
  • Gabriel C. Caponetti,
  • Luca Paruzzo,
  • Jaryse C. Harris,
  • Elise A. Chong,
  • Sandra P. Susanibar Adaniya,
  • Jakub Svoboda,
  • Sunita D. Nasta,
  • Ositadimma H. Ugwuanyi,
  • Daniel J. Landsburg,
  • Eugenio Fardella,
  • Adam J. Waxman,
  • Emeline R. Chong,
  • Vrutti Patel,
  • Raymone Pajarillo,
  • Irina Kulikovskaya,
  • David B. Lieberman,
  • Adam D. Cohen,
  • Bruce L. Levine,
  • Edward A. Stadtmauer,
  • Noelle V. Frey,
  • Dan T. Vogl,
  • Elizabeth O. Hexner,
  • Stefan K. Barta,
  • David L. Porter,
  • Alfred L. Garfall,
  • Stephen J. Schuster,
  • Carl H. June,
  • Marco Ruella

摘要

We report a T cell lymphoma (TCL) occurring 3 months after anti-CD19 chimeric antigen receptor (CAR) T cell immunotherapy for non-Hodgkin B cell lymphoma. The TCL was diagnosed from a thoracic lymph node upon surgery for lung cancer. The TCL exhibited CD8+ cytotoxic phenotype and a JAK3 variant, while the CAR transgene was very low. The T cell clone was identified at low levels in the blood before CAR T infusion and in lung cancer. To assess the overall risk of secondary primary malignancy after commercial CAR T (CD19, BCMA), we analyzed 449 patients treated at the University of Pennsylvania. At a median follow-up of 10.3 months, 16 patients (3.6%) had a secondary primary malignancy. The median onset time was 26.4 and 9.7 months for solid and hematological malignancies, respectively. The projected 5-year cumulative incidence is 15.2% for solid and 2.3% for hematological malignancies. Overall, one case of TCL was observed, suggesting a low risk of TCL after CAR T.