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同时患有B细胞非霍奇金淋巴瘤和风湿性自身免疫性疾病患者的CD19靶向嵌合抗原受体T细胞疗法:一项倾向评分匹配研究

CD19-targeted chimeric antigen receptor T-cell therapy in patients with concurrent B-cell Non-Hodgkin lymphoma and rheumatic autoimmune diseases: a propensity score matching study.

作者信息

Wang Jiasheng, Alkrekshi Akram, Dasari Srilatha, Lin Hsin-Ti Cindy, Elantably Dina, Armashi Abdul Rahman Al

机构信息

Department of Hematology and Oncology, Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.

Department of Internal Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, OH, USA.

出版信息

Bone Marrow Transplant. 2023 Nov;58(11):1223-1228. doi: 10.1038/s41409-023-02086-1. Epub 2023 Aug 21.

Abstract

Rheumatic autoimmune diseases not only involve the production of autoantibodies but also demonstrate T-cell dysfunction. In patients with concurrent B-cell non-Hodgkin lymphoma (NHL) and rheumatic autoimmune diseases, the safety and efficacy of CD19-targeted chimeric antigen receptor (CAR) T-cell therapy are unknown. Using an aggregated electronic health record database, patients with rheumatic autoimmune diseases (auto group) were compared to propensity score-matched patients without rheumatic autoimmune diseases (non-auto group). From 1/2019 to 1/2023, 58 (4.3%) of 1,363 patients who received CD19-targeted CAR T-cell therapy had concurrent rheumatic autoimmune diseases. Both groups had similar incidence, severity, and management of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Moreover, the two groups had similar time-to-next treatment or death (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.60 to 1.59, log-rank p = 0.91) and overall survival (HR 0.90, 95%CI 0.46 to 1.78, p = 0.76). Following CAR T-cell infusion, patients with rheumatic autoimmune diseases achieved decreased inflammatory markers, seronegative conversion of autoantibodies, as well as reduced use of steroids and disease-modifying anti-rheumatic drugs. In conclusion, the safety and efficacy of CAR T-cell therapy were not affected in patients with rheumatic autoimmune diseases. Moreover, they achieved better biochemical control of underlying rheumatic diseases.

摘要

风湿性自身免疫性疾病不仅涉及自身抗体的产生,还表现出T细胞功能障碍。在同时患有B细胞非霍奇金淋巴瘤(NHL)和风湿性自身免疫性疾病的患者中,靶向CD19的嵌合抗原受体(CAR)T细胞疗法的安全性和有效性尚不清楚。利用一个汇总的电子健康记录数据库,将风湿性自身免疫性疾病患者(自身免疫组)与倾向评分匹配的无风湿性自身免疫性疾病患者(非自身免疫组)进行比较。在2019年1月至2023年1月期间,1363例接受靶向CD19的CAR T细胞疗法的患者中有58例(4.3%)同时患有风湿性自身免疫性疾病。两组在细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)的发生率、严重程度和管理方面相似。此外,两组在下一次治疗或死亡时间(风险比[HR]0.97,95%置信区间[CI]0.60至1.59,对数秩p = 0.91)和总生存期(HR 0.90,95%CI 0.46至1.78,p = 0.76)方面相似。在CAR T细胞输注后,风湿性自身免疫性疾病患者的炎症标志物降低,自身抗体血清学转阴,同时类固醇和改善病情抗风湿药物的使用减少。总之,CAR T细胞疗法的安全性和有效性在风湿性自身免疫性疾病患者中不受影响。此外,他们对潜在的风湿性疾病实现了更好的生化控制。

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