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

• Published in: Nature medicine Vol. 30; no. 4; pp. 984 - 989
• Main Authors: Ghilardi, Guido, Fraietta, Joseph A., Gerson, James N., Van Deerlin, Vivianna M., Morrissette, Jennifer J. D., Caponetti, Gabriel C., Paruzzo, Luca, Harris, Jaryse C., Chong, Elise A., Susanibar Adaniya, Sandra P., Svoboda, Jakub, Nasta, Sunita D., Ugwuanyi, Ositadimma H., Landsburg, Daniel J., Fardella, Eugenio, Waxman, Adam J., Chong, Emeline R., Patel, Vrutti, Pajarillo, Raymone, Kulikovskaya, Irina, Lieberman, David B., Cohen, Adam D., Levine, Bruce L., Stadtmauer, Edward A., Frey, Noelle V., Vogl, Dan T., Hexner, Elizabeth O., Barta, Stefan K., Porter, David L., Garfall, Alfred L., Schuster, Stephen J., June, Carl H., Ruella, Marco
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2024; Nature Publishing Group
• Subjects: 631/67/1059/2325; 631/67/1990; 692/308/409; 706/648/697/129; B-cell lymphoma; Biomedical and Life Sciences; Biomedicine; Brief Communication; Cancer Research; CD19 antigen; CD8 antigen; Cell therapy; Chimeric antigen receptors; Cytotoxicity; Hematology; Immunotherapy; Infectious Diseases; Insertional mutagenesis; Lung cancer; Lymph nodes; Lymphocytes; Lymphocytes T; Lymphoma; Malignancy; Metabolic Diseases; Molecular Medicine; Neurosciences; Patients; Phenotypes; T-cell lymphoma; Thorax; Transgenes
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-024-02826-w

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. Profiling of a case of secondary T cell lymphoma following anti-CD19 CAR T cell therapy suggests that it was not caused by CAR insertional mutagenesis, with single-center analysis indicating that secondary T cell lymphoma risk after commercial CAR T cell treatment is low.