In a single-center study reported in The New England Journal of Medicine, Hamilton et al found that second tumors had occurred in 25 of 724 patients during 15 months of follow-up after receipt of chimeric antigen receptor (CAR) T-cell therapy, including one fatal case of T-cell lymphoma.
The study included 724 patients undergoing adoptive cellular CAR T-cell therapy at Stanford University Medical Center between February 2016 and January 2024.
Key Findings
After a median follow-up of 15 months, 25 second tumors had been identified, excluding nonmelanoma skin cancers. Among 14 hematologic second tumors, 13 were associated with myelodysplastic syndrome or acute myeloid leukemia, and 1, discussed below, was a T-cell lymphoma.
The cumulative incidence of a hematologic second tumor at 3 years was 6.5%. Among 11 second solid tumors, 4 were melanomas, 2 were prostate carcinomas, 2 were breast ductal carcinomas, 1 was endometrial adenocarcinoma, 1 was lung adenocarcinoma, and 1 was metastatic mesothelioma.
The second T-cell lymphoma was fatal in a patent who received axicabtagene ciloleucel for diffuse large B-cell lymphoma. The lymphomas had molecularly distinct immunophenotypes and genomic profiles; however, both were positive for Epstein-Barr virus and were associated with DNMT3A and TET2 mutant clonal hematopoiesis. No evidence to implicate oncogenic retroviral integration in the T-cell lymphoma was identified based on multiple assays to interrogate retroviral vector DNA, RNA, and protein at single-cell resolution.
The investigators concluded “Our results highlight the rarity of second tumors and provide a framework for defining clonal relationships and viral vector monitoring.”
Ash A. Alizadeh, MD, PhD, of Stanford Cancer Institute, Stanford University Medical Center, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the National Cancer Institute and others. For full disclosures of the study authors, visit nejm.org.
