Prognosis and Management of Secondary T-Cell Lymphoma in 17 Cases after CAR-T Cell Therapy

doi:10.19803/j.1672-8629.20250666

Abstract

Abstract: Objective To investigate the clinical outcomes of and management strategies for secondary T-cell lymphomas after chimeric antigen receptor T (CAR-T) cell therapy. Methods Such databases as Medline, Embase and the Cochrane Library were searched for literature that was published as of September 1, 2025 to analyze cases of secondary T-cell lymphomas following CAR-T cell therapy in general and the related pathogenesis, diagnostic and therapeutic approaches in particular. Results Seventeen cases of secondary T-cell lymphomas after CAR-T cell therapy were identified, with 11 cases being CAR positive T-cell lymphomas and 6 cases being CAR negative ones. There were 8 cases of secondary T-cell lymphomas after cilta-cel, including 7 cases of CAR positive T-cell lymphomas. There were 2 cases of CAR negative T-cell lymphomas after tisa-cel. There were 4 cases of CAR-T cell lymphomas after axi-cel. Among the three cases treated with CAR-T cell therapy for clinical research, there were two cases of CAR positive T-cell lymphomas. The incidence of secondary T-cell lymphomas after CAR-T cell therapy was below 1%. Molecular abnormalities with loss-of-function changes in TET2 (Ten–Eleven Translocation 2) were frequent in T-cell lymphomas, and were detected in 7 cases. CAR molecules could serve as persistent signals that directly promoted the proliferation and survival of malignant precursor T-cell clones. A few cases of aggressive T-cell lymphomas responded to multi-drug chemotherapy while indolent cases generally responded well to immunosuppressive treatments such as glucocorticoids or cyclosporine A. CAR T-cell lymphomas needed to be differentiated from CAR T-cell expansion. Diagnosis was made using PET-CT and biopsy. Multimodal analysis could help distinguish malignant T cells from healthy T cells, identify highly expressed targets, and verify them through flow cytometry along with other cytokines and receptors that promoted cell survival. Subsequently, suitable drugs could be selected based on in vitro drug screening and efficacy evaluation using biochemical markers and imaging. Conclusion The proportion of secondary T-cell lymphomas is the highest after cilta-cel. The risk of secondary T-cell lymphomas after CAR-T cell therapy remains unclear, so data on more rigorous large-sample case-control studies is needed. CAR T-cell lymphomas not only affect lymph nodes, but also tend to invade extralymphatic sites, particularly in the skin and gastrointestinal system. Lifelong follow-up is necessary, and early detection, early diagnosis, and early treatment are recommended. Combination therapies, immunosuppression, and targeted therapy, followed by hematopoietic stem cell transplantation after remission, may be effective.

Key words: CAR-T Cell Therapy, Second Primary Malignancies, Secondary T-Cell Lymphoma, Prognosis, Management strategies

CLC Number:

ZHANG Hao, HE Shujiao, WANG Yiran. Prognosis and Management of Secondary T-Cell Lymphoma in 17 Cases after CAR-T Cell Therapy[J]. Chinese Journal of Pharmacovigilance, 2025, 22(12): 1388-1393.

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