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

• Authors: 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
• Journal: Nature medicine (Nat Med) Vol. 30 Issue 4 Pg. 984-989 (Apr 2024) ISSN: 1546-170X [Electronic] United States
• PMID: 38266761 (Publication Type: Journal Article)
• Copyright: © 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chemical References

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

Topics

• Humans
• Immunotherapy, Adoptive (adverse effects)
• Receptors, Chimeric Antigen (genetics)
• Receptors, Antigen, T-Cell (genetics)
• Lymphoma, B-Cell
• Lymphoma, T-Cell
• Hematologic Neoplasms
• Lung Neoplasms
• Antigens, CD19