PO.CL05.01 · 临床研究
CAR T细胞治疗在中枢神经系统淋巴瘤中的安全性和疗效：一项荟萃分析
Safety and efficacy of CAR T-cell therapy in CNS lymphoma: A meta-analysis
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：鉴于关键性CAR T细胞试验中中枢神经系统(CNS)受累的代表性有限，嵌合抗原受体T细胞(CART)治疗在中枢神经系统淋巴瘤(CNSL)中的疗效和安全性仍不明确。本荟萃分析综合了评估接受CART治疗的原发性(PCNSL)和继发性中枢神经系统淋巴瘤(SCNSL)队列结局的研究数据。
方法：在PubMed、Scopus、Web of Science及临床注册库中进行了截至2025年6月的全面检索。纳入报告CNSL在CART治疗后疗效或毒性结局的研究。使用Freeman-Tukey双反正弦转换稳定比例，并采用逆方差加权进行合并。使用DerSimonian-Laird方法估计研究间异质性，并通过Jackson法计算τ²置信区间。根据I² ≥ 50%或< 50%分别应用随机效应或固定效应模型。使用Egger回归评估发表偏倚。亚组分析和多重荟萃回归分析评估了包括CNS类别(PCNSL、SCNSL或两者兼有)和发表年份在内的调节因素。
结果：对涵盖1,457名受试者的39项研究数据进行了荟萃分析。合并总体缓解率(ORR)为0.75 [95% CI: 0.70-0.79; I² = 52.2%]。完全缓解(CR)率为0.52 [95% CI: 0.46-0.58; I² = 63.0%]，部分缓解(PR)率为0.18 [95% CI: 0.14-0.22; I² = 50.40%]。未检测到显著的发表偏倚。荟萃回归表明发表年份或CNS类别对ORR无显著影响。细胞因子释放综合征(CRS)发生率为83.8% [95% CI: 79.1-88.2; I² = 71.4%]，其中≥3级CRS为5.74% [95% CI: 3.21-8.76; I² = 62.1%]。免疫效应细胞相关神经毒性综合征(ICANS)报告率为44.4% [95% CI: 35.9-53.1; I² = 86.5%]，其中重度(≥3级)事件为16.8% [95% CI: 11.9-22.4; I² = 74.3%]。
结论：CART治疗在CNS淋巴瘤中实现了强劲的缓解率，PCNSL与SCNSL之间疗效相当。神经毒性仍然频繁但可控，重度CRS事件不常见。
查看英文原文 English abstract
Background: The efficacy and safety of Chimeric Antigen Receptor T-cell (CART) therapy in Central Nervous System Lymphoma (CNSL) remain uncertain, given the limited representation of CNS involvement in pivotal CAR T-cell trials. This meta-analysis synthesized data from studies evaluating outcomes in both primary (PCNSL) and secondary CNS lymphoma (SCNSL) cohorts treated with CART.
Methods: A comprehensive search was performed across PubMed, Scopus, Web of Science, and clinical registries up to June 2025. Studies reporting efficacy or toxicity outcomes in CNSL following CART therapy were included. Proportions were stabilized using the Freeman-Tukey double arcsine transformation and pooled using inverse variance weighting. Between-study heterogeneity was estimated with the DerSimonian-Laird method, and τ² confidence intervals were calculated via the Jackson approach. Random- or fixed-effects models were applied based on I² ≥ 50% or < 50%, respectively. Publication bias was assessed using Egger's regression. Subgroup and multiple meta-regression analyses evaluated moderators including CNS category (PCNSL, SCNSL, or Both) and publication year.
Results: Data from thirty-nine studies encompassing 1,457 participants were meta-analyzed. The pooled overall response rate (ORR) was 0.75 [95% CI: 0.70-0.79; I² = 52.2%]. Complete response (CR) rate was 0.52 [95% CI: 0.46-0.58; I² = 63.0%], and partial response (PR) rate 0.18 [95% CI: 0.14-0.22; I² = 50.40%]. No significant publication bias was detected. Meta-regression indicated no significant effect of publication year or CNS category on ORR. Cytokine Release Syndrome (CRS) occurred in 83.8% [95% CI: 79.1-88.2; I² = 71.4%], with grade ≥3 CRS in 5.74% [95% CI: 3.21-8.76; I² = 62.1%]. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported in 44.4% [95% CI: 35.9-53.1; I² = 86.5%], with severe (grade ≥3) events in 16.8% [95% CI: 11.9-22.4; I² = 74.3%].
Conclusions: CART therapy achieves robust response rates in CNS lymphoma, with efficacy comparable between PCNSL and SCNSL. Neurotoxicity remains frequent but manageable, and severe CRS events are infrequent.
利益披露 Disclosure
A. Shawabkeh, None..
M. I. Alsufi, None..
H. AbuHashesh, None..
H. Khreisat, None..
Z. Muhanna, None..
S. Salman, None..
A. Obeid, None..
L. AlDaher, None..
J. Yasin, None.