Dulery Remy, Guiraud Vincent, Choquet Sylvain, Thieblemont Catherine, Bachy Emmanuel, Barete Stéphane, Todesco Ève, Arnulf Bertrand, Boissel Nicolas, Baruchel André, Bay Jacques-Olivier, Le Gouill Steven, Houot Roch
Department of Clinical Hematology and Cellular Therapy, Sorbonne University, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, INSERM, UMRs 938, Centre de recherche Saint-Antoine (CRSA), Paris, France.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nat Med. 2025 Apr;31(4):1130-1133. doi: 10.1038/s41591-024-03458-w. Epub 2025 Jan 8.
The risk of T cell malignancies after chimeric antigen receptor (CAR) T cell therapy is a concern, although the true incidence remains unclear. Here we analyzed the DESCAR-T registry database, encompassing all pediatric and adult patients with hematologic malignancies who received CAR T cell therapy in France since 1 July 2018. Of the 3,066 patients included (2,536 B cell lymphoma, 162 B cell acute lymphoblastic leukemia (ALL) and 368 multiple myeloma), 1,680 (54.8%) received axicabtagene ciloleucel, 205 (6.7%) brexucabtagene autoleucel, 44 (1.4%) lisocabtagene maraleucel and 769 (25.1%) tisagenlecleucel. All multiple myeloma patients received idecabtagene vicleucel, with none receiving ciltacabtagene autoleucel. After a median follow-up of 12.7 months for B cell lymphoma, 17.7 months for B cell ALL and 6.3 months for multiple myeloma, only one (0.03%) patient developed a T cell malignancy after CAR T infusion. Specifically, the patient was diagnosed with a primary cutaneous CD30 T cell lymphoproliferative disorder (anaplastic lymphoma kinase-negative) 3 years after receiving tisagenlecleucel therapy for diffuse large B cell lymphoma. This was associated with the integration of a CAR clone into the tumor suppressor gene PLAAT4 (phospholipase A and acyltransferase 4). Thus, the development of this secondary T cell malignancy might be linked to the use of CAR T cell therapy. In conclusion, our findings indicate a very low risk of T cell malignancy after CAR T cell therapy.
嵌合抗原受体（CAR）T细胞疗法后发生T细胞恶性肿瘤的风险令人担忧，尽管其真实发病率仍不清楚。在此，我们分析了DESCAR-T注册数据库，该数据库涵盖了自2018年7月1日起在法国接受CAR T细胞疗法的所有血液系统恶性肿瘤的儿科和成年患者。在纳入的3066例患者中（2536例B细胞淋巴瘤、162例B细胞急性淋巴细胞白血病（ALL）和368例多发性骨髓瘤），1680例（54.8%）接受了axi-cabtagene ciloleucel，205例（6.7%）接受了brexucabtagene autoleucel，44例（1.4%）接受了lisocabtagene maraleucel，769例（25.1%）接受了tisagenlecleucel。所有多发性骨髓瘤患者均接受了idecabtagene vicleucel，无人接受cilta-cabtagene autoleucel。B细胞淋巴瘤的中位随访时间为12.7个月，B细胞ALL为17.7个月，多发性骨髓瘤为6.3个月，只有1例（0.03%）患者在CAR T输注后发生了T细胞恶性肿瘤。具体而言，该患者在接受tisagenlecleucel治疗弥漫性大B细胞淋巴瘤3年后，被诊断为原发性皮肤CD30 T细胞淋巴增殖性疾病（间变性淋巴瘤激酶阴性）。这与一个CAR克隆整合到肿瘤抑制基因PLAAT4（磷脂酶A和酰基转移酶4）中有关。因此，这种继发性T细胞恶性肿瘤的发生可能与CAR T细胞疗法的使用有关。总之，我们的研究结果表明CAR T细胞疗法后发生T细胞恶性肿瘤的风险非常低。
