Background
Secondary cancer risk after CAR T-cell therapy is an emerging concern, especially T-cell neoplasms related to viral vector integration.
Methods
The clinical experience with adoptive cellular CAR therapy at Stanford since 2016 was reviewed and the occurrence of second malignancies ascertained. In one case of secondary T-cell lymphoma, a broad array of molecular, genetic, and cellular techniques were used to interrogate the tumor, the CAR-T cells, and the normal hematopoietic cells in the patient.
Results
We describe the second cancer risk in 724 patients receiving T-cell therapies at our center. We identified a lethal T-cell lymphoma after axicabtagene ciloleucel therapy for DLBCL, and deeply profiled both tumors. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were EBV+ and associated with DNMT3A and TET2 mutant clonal hematopoiesis. We found no evidence of oncogenic retroviral integration using multiple techniques.
Conclusion
These results highlight the rarity of secondary neoplasms, while providing a framework for defining clonal relationships and viral vector monitoring.
(Funded by NCI and others.)