CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Real-world evidence of the safety and survival with CD19 CAR-T cell therapy for relapsed/refractory solid organ transplant-related PTLD.
Real-world evidence of the safety and survival with CD19 CAR-T cell therapy for relapsed/refractory solid organ transplant-related PTLD.
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CD19 CAR-T 细胞疗法用于复发/难治性实体器官移植(SOT)相关移植后淋巴增殖性疾病(PTLD)的应用尚未得到充分研究。
我们开展了一项针对复发/难治性 SOT 相关 PTLD 成人患者的多中心回顾性分析。在 22 例复发/难治性 SOT-PTLD 患者中,病理类型为单形性 B 细胞。既往 SOT 包括 14 例肾脏(64%)、3 例肝脏(14%)、2 例心脏(9%)、1 例肠道(5%)、1 例肺(5%)以及 1 例肾移植后胰腺移植(5%)。从 SOT 到 PTLD 诊断的中位时间为 107 个月。55% 的患者使用了 CAR-T 前桥接治疗,64% 的患者在 CAR-T 输注前完全停用了免疫抑制。18 例(82%)患者发生了细胞因子释放综合征:1 级(G)3 和 G4 各 1 例(5%)。16 例(73%)患者观察到免疫效应细胞相关神经毒性综合征:6 例(27%)为 G3,2 例(9%)为 G4。总缓解率为 64%(55% 完全缓解)。3 例(14%)患者在 CAR-T 后发生了移植物排斥反应。2 年无进展生存率和总生存率分别为 35% 和 58%。
此外,CAR-T 后达到 CR 与生存密切相关。总体而言,CD19 CAR-T 疗法在复发/难治性 SOT 相关 PTLD 中的安全性和疗效似乎与关键性 CAR-T 数据相似,包括约三分之一的患者获得持续缓解。
The use of CD19 chimeric antigen receptor T-cell (CAR-T) therapy for relapsed/refractory solid organ transplantation (SOT)-related post-transplant lymphoproliferative disorder (PTLD) is not well studied.
We conducted a multicentre, retrospective analysis of adults with relapsed/refractory SOT-associated PTLD. Among 22 relapsed/refractory SOT-PTLD patients, the pathology was monomorphic B cell. Prior SOTs included 14 kidney (64%), three liver (14%), two heart (9%), one intestinal (5%), one lung (5%), and one pancreas after kidney transplant (5%). The median time from SOT to PTLD diagnosis was 107 months. Pre-CAR-T bridging therapy was used in 55% of patients, and immunosuppression was stopped completely before CAR-T infusion in 64%.
Eighteen (82%) patients experienced cytokine release syndrome: one (5%) each grade (G) 3 and G4. The immune effector cell-associated neurotoxicity syndrome was observed in 16 (73%) patients: six (27%) G3 and two (9%) G4. The overall response rate was 64% (55% complete response). Three patients (14%) experienced allograft rejection after CAR-T. The two-year progression-free survival and overall survival rates were 35% and 58%, respectively.
Additionally, the achievement of CR post-CAR-T was strongly associated with survival. Collectively, the safety and efficacy of CD19 CAR-T therapy in relapsed/refractory SOT-related PTLD appeared similar to pivotal CAR-T data, including approximately one-third of patients achieving sustained remission.
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