Rare but Real: Understanding Secondary Cancers After CAR T-Cell Therapy and What It Means for Future Treatments

Secondary cancers, particularly T-cell lymphomas, are an emerging concern following chimeric antigen receptor (CAR) T-cell therapy, especially due to potential viral vector integration causing oncogenesis. However, the risk and mechanisms of such secondary malignancies remain understudied.

In this study, researchers reviewed the clinical experience with adoptive CAR T-cell therapy at Stanford since 2016, analyzing 724 patients to ascertain the occurrence of second malignancies. In one case of a secondary T-cell lymphoma following CAR T-cell therapy for diffuse large B-cell lymphoma (DLBCL), they employed a broad array of molecular, genetic, and cellular techniques to investigate the tumor, the CAR T cells, and the patient’s normal hematopoietic cells.

They found that secondary T-cell lymphomas after CAR T-cell therapy are rare, identifying only one case among 724 patients. This particular T-cell lymphoma was molecularly distinct from the original DLBCL but both were EBV-positive and associated with DNMT3A and TET2 mutant clonal hematopoiesis. Importantly, they found no evidence of oncogenic retroviral integration in the T-cell lymphoma, suggesting that the secondary cancer was not caused by the CAR T-cell therapy vector. These findings highlight the rarity of secondary neoplasms after CAR T-cell therapy and provide a framework for monitoring and understanding clonal relationships and viral vector integration in such cases.

This research was published in the New England Journal of Medicine. This article of Mark P. Hamilton at the Stanford University School of Medicine can be found here, DOI: 10.1056/NEJMoa2401361

This image shows a microscopic view of lymphoma cells that are diffusely positive for EBER. Contributed by Roberto N. Miranda, M.D. and Carlos A. Torres-Cabala, M.D.

Image citation: Marques-Piubelli ML, Torres-Cabala CA, Miranda RN. Extranodal NK / T cell lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBnasal.html. Accessed October 29th, 2024.

This post was made with love by our editor-in-chief @ekang78

#GESRI#democratizescience#cells#cancer#leukemia#hematology#immunotherapy#science