Abstract
The risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, especially the risk of T-cell neoplasms related to viral vector integration, is an emerging concern. We reviewed our clinical experience with adoptive cellular CAR T-cell therapy at our institution since 2016 and ascertained the occurrence of second tumors. 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. A total of 724 patients who had received T-cell therapies at our center were included in the study. A lethal T-cell lymphoma was identified in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma, and both lymphomas were deeply profiled. Each lymphoma had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated withandmutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring. (Funded by the National Cancer Institute and others.).
Overview
- The study focuses on the risk of second tumors after chimeric antigen receptor (CAR) T-cell therapy, specifically the risk of T-cell neoplasms related to viral vector integration. The study reviews clinical experience with adoptive cellular CAR T-cell therapy at the institution since 2016 and ascertains the occurrence of second tumors. The study includes 724 patients who had received T-cell therapies at the center and identifies a lethal T-cell lymphoma in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma. The study aims to provide a framework for defining clonal relationships and viral vector monitoring.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions, specifically the risk of second tumors after CAR T-cell therapy. The study identifies a lethal T-cell lymphoma in a patient who had received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma. The study finds that both lymphomas had molecularly distinct immunophenotypes and genomic profiles, but both were positive for Epstein-Barr virus and were associated with and mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. The study highlights the rarity of second tumors and provides a framework for defining clonal relationships and viral vector monitoring.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice, as they provide a framework for defining clonal relationships and viral vector monitoring. The study identifies the rarity of second tumors after CAR T-cell therapy, which is an emerging concern. The study suggests that future research should focus on developing more effective strategies for monitoring viral vector integration and minimizing the risk of T-cell neoplasms related to viral vector integration. The study also suggests that future research should explore the use of novel approaches for defining clonal relationships and viral vector monitoring.