CAR-T细胞治疗后继发T细胞淋巴瘤的预后与诊疗分析

doi:10.19803/j.1672-8629.20250666

摘要/Abstract

摘要： 目的研究嵌合抗原受体（CAR）T细胞治疗后继发T细胞淋巴瘤的临床预后和诊疗策略。方法根据PRISMA 指南,系统检索Medline、Embase、Cochrane等数据库,自建库至2025年9月1日,收集CAR-T细胞治疗继发T细胞淋巴瘤病例,分析CAR+T细胞治疗后T细胞淋巴瘤的发病机制、诊疗策略和风险防控。结果 17例CAR-T细胞治疗后继发T细胞淋巴瘤病例中,11例为CAR+T细胞淋巴瘤,6例为CAR-T细胞淋巴瘤。Cilta-cel治疗后8例继发T细胞淋巴瘤,其中CAR+T细胞淋巴瘤7例。Tisa-cel治疗后2例CAR+T细胞淋巴瘤。Axi-cel治疗后4例CAR-T细胞淋巴瘤。3例临床研究CAR-T细胞治疗后包括2例CAR+T细胞淋巴瘤。CAR-T细胞治疗后继发T细胞淋巴瘤发生率在1%以下。CAR+T细胞淋巴瘤中分子异常TET2功能缺失性改变反复出现,7例病例检测到该变异。CAR分子可作为持续性信号,直接促进恶性前T细胞克隆的扩增与存活。少数侵袭性T细胞淋巴瘤病例对多药化疗有应答,惰性病例往往对糖皮质激素或环孢素A等免疫抑制剂治疗反应良好。CAR+T细胞淋巴瘤需要与CAR+T细胞扩增需鉴别诊断,PET-CT与活检进行诊断,多模态分析区分恶性T细胞和健康T细胞,识别出高表达的靶点,再根据体外药物筛选、基于生化指标与影像学的疗效评估选择合适的药物。结论 Cilta-cel治疗后继发T细胞淋巴瘤占比最高。CAR-T细胞治疗后继发T细胞淋巴瘤风险未定,需更严谨的大样本病例对照研究数据。CAR+T细胞淋巴瘤不仅累及淋巴结,更具有结外侵犯的倾向,尤其好发于皮肤及胃肠道系统。需终身随访,治疗上遵循早发现、早诊断、早治疗的原则,多药联合化疗、免疫抑制、靶向治疗等缓解后联合造血干细胞移植可能有效。

关键词: CAR-T细胞治疗, 第二原发恶性肿瘤, 继发T细胞淋巴瘤, 预后, 诊疗策略

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

中图分类号:

张颢, 贺淑娇, 王怡然. CAR-T细胞治疗后继发T细胞淋巴瘤的预后与诊疗分析[J]. 中国药物警戒, 2025, 22(12): 1388-1393.

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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