Second Tumors Rare Post CAR T-Cell Therapy

Second tumors are rarely observed following chimeric antigen receptor (CAR) T-cell therapy, based on findings published in the June 13, 2024 issue of the New England Journal of Medicine.

Dr. Mark P. Hamilton and his team from Stanford University, California, investigated the development of secondary tumors post-CAR T-cell therapy since 2016. Their study utilized a wide range of molecular, genetic, and cellular methodologies to examine the tumor, CAR T cells, and normal hematopoietic cells in a patient who developed secondary T-cell lymphoma.

The study encompassed 724 patients treated with T-cell therapies at their institution. Within this cohort, the researchers detected a fatal T-cell lymphoma in a patient who previously received axicabtagene ciloleucel therapy for diffuse large B-cell lymphoma. Detailed profiling was conducted on both lymphomas, revealing that each had distinct molecular characteristics and unique genomic profiles. Both lymphomas were linked to DNMT3A and TET2 mutant clonal hematopoiesis and tested positive for Epstein-Barr virus. The application of various investigative techniques did not show any evidence of oncogenic retroviral integration.

The authors of the study highlighted, “In our index case, despite exhaustive genetic profiling, we found no evidence of CAR T-cell vector integration into the T-cell lymphoma or any indication of CAR expression.”