Review examines 18 reported T-cell lymphomas following CAR T-cell therapy

A review in Blood Advances evaluated 18 reported cases of T-cell lymphoma following chimeric antigen receptor (CAR) T-cell therapy. The authors examined clinical characteristics, lymphoma subtypes, immunophenotypes, genomic alterations, and CAR transgene expression to explore whether and how treatment might contribute to lymphomagenesis.

Cases occurred across the underlying hematologic malignancies and widely used commercial CAR T-cell products covered by the review. Most lymphomas showed aberrant CD4 and/or CD8 expression patterns. CAR transgenes were detected in lymphoma cells in 63% of evaluated cases (10/16), and integration into a known tumor suppressor gene or oncogene was reported in 73% (8/11). Frequently detected mutations involved the epigenetic regulators TET2 and DNMT3A and the JAK–STAT signaling pathway, particularly JAK3.

The authors describe potentially complex, multifactorial mechanisms, including preexisting clonal hematopoiesis, malignant transformation of CAR T cells, immune dysregulation, and lymphodepletion chemotherapy. These findings characterize a rare reported safety concern rather than quantify its frequency. The reported-case design and differing denominators for molecular analyses limit causal interpretation and comparisons between products. Only the abstract was available for this assessment.