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CD19 CAR-T 细胞治疗复发/难治性实体器官移植相关 PTLD 的安全性和生存的真实世界证据

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.

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Real-world evidence of the safety and survival with CD19 CAR-T cell therapy for relapsed/refractory solid organ transplant-related PTLD.

PubMed 2023/05/02(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

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中文摘要

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。

展开英文摘要原文

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.

论文信息

作者
McKenna M、Epperla N、Ghobadi A、Liu J、Lazaryan A、Ibrahim U、Jacobson CA、Naik SG
单位
Division of Blood Disorders, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.United States
期刊
British journal of haematology2023 Jul
原文标识
PubMed 37129856 · DOI 10.1111/bjh.18828