Chimeric antigen receptor T-cell therapy and bispecific antibody sequence for large B-cell lymphoma: a systematic review and meta-analysis.

We aimed to assess through meta-analysisthe comparative effectiveness of bispecific antibodies (BsAb) after chimeric antigen receptor T-cell therapy (CAR-T) or CAR-T after BsAb.

我们旨在通过荟萃分析评估双特异性抗体（BsAb）在嵌合抗原受体T细胞疗法（CAR-T）之后或CAR-T在BsAb之后的相对有效性。

Methods

We performed a systematic reviewand meta-analysisby searching MEDLINE and Embase from Jan 1, 2010, until Sept 16, 2025, and haematological conferences in 2024 and 2025 for studies assessing effectiveness of BsAb monotherapy or combination therapy after CAR-T and CAR-T after BsAb.

我们通过检索MEDLINE和Embase数据库，从2010年1月1日起至2025年9月16日止，以及2024年和2025年的血液学会议，进行了一项系统综述和荟萃分析，评估了BsAb单药治疗或联合治疗在CAR-T之后以及CAR-T在BsAb之后的有效性。

We assessed summary data from published studies and abstracts for survival endpoints, response outcomes, and adverse events (cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome).

我们评估了已发表研究和摘要中的汇总数据，包括生存终点、反应结果以及不良事件（细胞因子释放综合征和免疫效应细胞相关神经毒性综合征）。

We performed an indirect comparison of pooled estimates from separate studies (retrospective studies and single-arm clinical trials) by an inverse variance random-effects meta-analysis.

我们通过逆方差随机效应荟萃分析，对单独研究（回顾性研究和单臂临床试验）的汇总估计进行了间接比较。

We used the Joanna Briggs Institute and Methodological Index for Non-Randomised Studies checklists for bias assessment.

我们使用了Joanna Briggs研究所和非随机化研究方法学指数清单进行偏差评估。

This study is registered with PROSPERO (CRD420251071424).

该研究已在PROSPERO注册（CRD420251071424）。

Results

2122 patients were included across 15 clinical trials and 15 retrospective studies, drawn from 14 haematology conference abstracts and 19 full text articles.

该研究纳入了2122名患者，这些患者来自15项临床试验和15项回顾性研究，这些研究资料来源于14个血液学会议摘要和19篇全文文章。

Five studies represented 113 patients for CAR-T after BsAb, 20 studies represented 737 patients for BsAb after CAR-T, and five studies included BsAb combination treatments after CAR-T with 125 patients.

五项研究代表了113名接受BsAb后CAR-T治疗的患者，20项研究代表了737名接受CAR-T后BsAb治疗的患者，五项研究包括了125名接受CAR-T后BsAb联合治疗的患者。

In studies that reported demographic information (27 of 28 studies), the mean or median age ranged from 48 to 73 years.

在报告人口统计信息的28项研究中（27项研究提供了这些信息），平均或中位年龄范围从48岁到73岁。

We found a pooled complete response rate for CAR-T after BsAb of 53·7% (95% CI 39·8-67·0; I2 =38·0%; four studies [n=101]) compared with 29·4% (25·1-34·0; 34·8%; 18 studies [n=680]; p=0·0008) for BsAb after CAR-T.

我们发现，在 BsAb 后 CAR-T 的完全缓解率汇总为 53.7%（95% 置信区间 39.8-67.0；I2=38.0%；四项研究[n=101]），而 BsAb 在 CAR-T 后的完全缓解率则为 29.4%（25.1-34.0；34.8%；18 项研究[n=680]；p=0.0008）。

When excluding abstracts from conferences the pooled complete response rate for BsAb after CAR-T was 28·1% (95% CI 23·3-33·4 I2 =33·3%, 12 studies [n=511]).

在排除会议摘要后，BsAb 在 CAR-T 后的完全缓解率汇总为 28.1%（95% 置信区间 23.3-33.4；I2=33.3%，12 项研究[n=511]）。

The pooled complete response rate for BsAb combination after CAR-T was 46·4% (37·9-55·2; I2 =0·0%; five studies [n=125]) compared with 29·4% (25·1-34·0; I2 =34·8%; 18 studies [n=680]; p=0·0005) for BsAb monotherapy after CAR-T.

BsAb组合疗法在CAR-T治疗后的完全缓解率为46.4%（95% 置信区间 37.9-55.2；I2=0.0%；五项研究[n=125]），而 BsAb单药疗法在CAR-T治疗后的完全缓解率为29.4%（95% 置信区间 25.1-34.0；I2=34.8%；18项研究[n=680]；p=0.0005）

Finally, we found an improved objective response ratein patients treated with CAR-T after BsAb compared with patients treated with CAR-T without previous BsAb exposure (pooled risk ratio of 1·62 [95% CI 1·24-2·11]; two studies [n=57, n=64]; p=0·0004).

最后，我们发现接受CAR-T治疗后 BsAb治疗的患者与未接受 BsAb治疗的 CAR-T患者相比，客观缓解率有所提高（风险比为1.62 [95% 置信区间 1.24-2.11]；两项研究[n=57, n=64]；p=0.0004）

interpretation

Based on current evidence, our meta-analysissuggests that BsAb therapy before CAR-T could improve future CAR-T effectiveness for large B-cell lymphoma, although our conclusions are limited by small sample sizes.

基于当前证据，我们的荟萃分析表明，在CAR-T治疗前使用BsAb治疗可以提高未来CAR-T对大B细胞淋巴瘤的疗效，尽管我们的结论受到样本量小的限制。

Nonetheless, our findings have important implications for the design of randomised controlled trials to identify the optimal treatment sequence of CAR-T and BsAb.

然而，我们的发现对于设计随机对照试验以确定CAR-T和BsAb的最佳治疗顺序具有重要意义。

funding

None.

无。