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

in Nature medicine by 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

TLDR

  • A study investigated the risk of secondary primary malignancy after CAR T therapy in 449 patients and found a 3.6% incidence of secondary malignancies, with one case of T cell lymphoma observed.
  • The projected 5-year cumulative incidence of solid and hematological malignancies was 15.2% and 2.3%, respectively.
  • These findings suggest a low risk of T cell lymphoma after CAR T therapy.

Abstract

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 CD8cytotoxic 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.

Overview

  • This study reports a case of 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, and exhibited CD8cytotoxic phenotype and a JAK3 variant.
  • The study aims to assess the overall risk of secondary primary malignancy after commercial CAR T (CD19, BCMA) treatment and examine the prevalence of TCL as a result.

Comparative Analysis & Findings

  • The study analyzed 449 patients treated at the University of Pennsylvania and found 16 patients (3.6%) had a secondary primary malignancy.
  • The median onset time for secondary solid and hematological malignancies was 26.4 and 9.7 months, respectively, and the projected 5-year cumulative incidence was 15.2% and 2.3%, respectively.
  • One case of TCL was observed, suggesting a low risk of TCL after CAR T treatment.

Implications and Future Directions

  • These findings highlight the importance of long-term monitoring for secondary primary malignancies in patients receiving CAR T therapy.
  • Future studies should focus on identifying risk factors for secondary primary malignancies and developing strategies to mitigate this risk.
  • Ongoing monitoring of patients receiving CAR T therapy will help elucidate the true incidence and prognosis of secondary primary malignancies.
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