Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy
Mark Hamilton, Takeshi Sugio, Troy Noordenbos, Shuyu Shi, Philip L. Bulterys, Chih Long Liu, Xiaoman Kang, Mari Olsen, Zinaida Good, Saurabh Dahiya, Matthew Frank, Bita Sahaf, Crystal L. Mackall, Dita Gratzinger, Maximilian Diehn, Ash A. Alizadeh, David B. Miklos
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: mutant clonal hematopoiesis. No evidence of oncogenic retroviral integration was found with the use of multiple techniques. CONCLUSIONS: 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.).