CAR T-cell therapy and the risk of secondary cancers
Hamilton MP, Sugio T, Noordenbos T, et al. Risk of Second Tumors and T-Cell Lymphoma After CAR T-Cell Therapy. New England Journal of Medicine. 2024; 390 (22): 2047 (doi: 10.1056/NEJMoa2401361).
Results of a single-site analysis suggest that despite emerging concern over the potential for secondary tumors and T-cell lymphoma following chimeric antigen receptor (CAR) T-cell infusion, such events occur infrequently. Investigators reviewed the cases of 724 patients who had undergone T-cell treatment at their facility since 2016. There was one instance of T-cell lymphoma that developed after administration of axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma. Aided by a range of molecular, genetic, and cellular techniques, scientists examined the patient's tumor cells, CAR T cells, and normal hematopoietic cells. The primary and secondary cancers had different molecular and genomic characteristics, but both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. However, there were no signs that oncogenic retroviral integration had occurred. This study provides a framework for defining clonal relationships and viral vector monitoring, the researchers write.