[The risk and management strategies for second primary tumor after CAR-T cell therapy]

Chimeric antigen receptor T (CAR-T) cell therapy has revolutionized the treatment of refractory hematologic malignancies, but its long-term safety has become an increasing concern. Secondary primary malignancies (SPM) following CAR-T-cell therapy have emerged as a growing focus of clinical and translational research. Evidence to date suggests that the incidence of different types of SPMs vary, with a two-year cumulative incidence ranging from approximately 0.08% to 8% and a median time to onset of 9.7 to 26.4 months, predominantly involving myeloid malignancies such as myelodysplastic syndromes and acute myeloid leukemia, while solid tumors and rare T-cell lymphomas have also been reported. CAR transgenes have been detected in only a minority of T-cell lymphoma cases. The mechanisms involved vector-related genomic integration risks, genotoxic stress from prior chemotherapy or hematopoietic stem cell transplantation, immune dysregulation, and clonal hematopoietic expansion. Future research may focus on developing safer gene-editing technologies, moving CAR-T-cell therapy to earlier treatment lines to reduce cumulative toxicity from prior therapies, implementing genetic risk screening before treatment, and establishing long-term systematic monitoring after therapy. By optimizing full-process management, the risk of SPM can be minimized, thereby improving the long-term safety of CAR-T-cell therapy while maintaining its therapeutic efficacy.