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CD19 特异性 CAR-T 细胞治疗继发性中枢神经系统淋巴瘤的疗效与安全性

英文原题:Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma.

PubMed 2022/08/19(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

研究概要

在此,我们回顾性分析了15例接受CD19特异性CAR-T细胞治疗的R/R继发性CNSL患者。

中文摘要

在复发/难治性(R/R)B细胞淋巴瘤中,CAR-T(CAR-T)细胞治疗已取得令人鼓舞的缓解。CAR-T细胞在中枢神经系统淋巴瘤(CNSL)中的疗效和安全性仍不明确。在此,我们回顾性分析了15例接受CD19特异性CAR-T细胞治疗的R/R继发性CNSL患者。患者在环磷酰胺和氟达拉滨预处理方案后输注CD19、CD19/CD20或CD19/CD22 CAR-T细胞。总缓解率为73.3%(11/15),其中9例(60%)达到完全缓解(CR),2例(13.3%)达到部分缓解(PR)。在中位随访12个月期间,中位无进展生存期(PFS)为4个月,中位总生存期(OS)为9个月。在12例伴有全身肿瘤浸润的患者中,7例(58.3%)在CNS中达到CR,5例(41.7%)在全身和CNS中均达到CR。CNS和全身疾病的中位DOR分别为8个月和4个月。在观察终点时,7例达到CNS疾病CR的患者中,1例仍存活,CNS疾病和全身疾病均持续CR。其余6例死于全身进展。在15例患者中,11例(73.3%)发生1-2级CRS,无患者发生3-4级CRS。免疫效应细胞相关神经毒性综合征(ICANS)发生于3例(20%)患者,包括1例(6.6%)4级ICANS。所有CRS或ICANS均可控制。基于其抗肿瘤效应和可接受的副作用特征,CD19特异性CAR-T细胞治疗似乎是继发性CNSL的一种有前景的治疗方法,同时需要更多策略来维持缓解。

展开英文摘要原文

Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response.

论文信息

作者
Zhang H、Yan Z、Wang Y、Qi Y、Hu Y、Li P、Cao J、Zhang M
单位
Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 36059496 · DOI 10.3389/fimmu.2022.965224