Treatment-related adverse events of CD3-based T cell-engaging bispecific antibodies in patients with cancer: a meta-analysis of clinical trials.

As these agents enter practice, it is essential to systematically characterise and summarise the range of treatment-related adverse events associated with these antibodies.

随着这些药物进入临床实践，系统地描述和总结与这些抗体相关的治疗相关不良事件的范围变得至关重要。

Methods

We conducted a meta-analysisby searching Cochrane, Embase, PubMed, and Web of Science for English-language clinical trials worldwide reporting treatment-related adverse events in patients receiving CD3-based T cell-engaging bispecific antibodies for cancer, published up to July 31, 2025.

我们通过检索Cochrane、Embase、PubMed和Web of Science，对截至2025年7月31日发表的全球英语临床试验进行了荟萃分析，这些试验报告了接受基于CD3的T细胞双特异性抗体治疗的癌症患者的治疗相关不良事件。

The primary outcomes were the overall incidenceof treatment-related adverse events, and toxicity profiles (ie, the incidenceof each specified adverse event, for both all-grade and grade 3 or worse treatment-related adverse events).

主要结果是治疗相关不良事件的总发生率，以及毒性特征（即，每种指定不良事件的发生率，包括所有级别的不良事件和3级或更严重的治疗相关不良事件）。

Pooled overall incidenceand profile estimates with 95% CIs for both all-grade and grade 3 or worse treatment-related adverse events were calculated using logit-transformed random-effects models.

使用对数变换的随机效应模型计算了所有级别和3级或更严重的治疗相关不良事件的总发生率及特征估计值，并给出了95%置信区间。

Heterogeneity across studies was quantified with the I2 statistic.

通过I2统计量量化了研究间的异质性。

The study is registered at PROSPERO (CRD420251130333).

该研究已在PROSPERO注册（CRD420251130333）。

Results

A total of 104 clinical trials enrolling 10 353 patients (7311 with haematological malignancies and 3042 with solid tumours) were included.

共纳入了104项临床试验，涉及10,353名患者（其中7,311名患有血液系统恶性肿瘤，3,042名患有实体瘤）。

For haematological malignancies, the overall incidenceof all-grade treatment-related adverse events was 97·5% (95% CI 95·2-98·7; I2=88·2%), and 70·3% (62·6-77·0; I2=94·4%) for grade 3 or worse adverse events.

对于血液恶性肿瘤，所有级别治疗相关不良事件的总发生率为97.5%（95%置信区间95.2-98.7；I2=88.2%），3级或更严重的不良事件发生率为70.3%（62.6-77.0；I2=94.4%）。

For solid tumours, corresponding incidences were 97·9% (95·7-99·0; I2=57·0%) and 45·3% (38·4-52·4; I2=87·0%), respectively.

对于实体瘤，相应的发生率分别为97.9%（95.7-99.0；I2=57.0%）和45.3%（38.4-52.4；I2=87.0%）。

The most frequently observed all-grade treatment-related adverse events were cytokine release syndrome in haematological malignancies (43·3% [95% CI 33·9-53·1]) and solid tumours (46·3% [25·5-67·1]).

观察到的最常见与治疗相关的所有级别不良事件是血液恶性肿瘤中的细胞因子释放综合征（43.3% [95% 置信区间 33.9-53.1]）和实体瘤（46.3% [25.5-67.1]）。

The most frequent grade 3 or worse treatment-related adverse events were neutropenia (18·1% [11·1-26·9]) in haematological cancers and increased γ-glutamyltransferase (3·68% [0·86-6·98]) in solid tumours.

与治疗相关的最常见3级或更严重的不良事件是血液癌症中的中性粒细胞减少症（18.1% [11.1-26.9]）和实体瘤中的γ-谷氨酰转移酶增加（3.68% [0.86-6.98]）。

Treatment-related deaths occurred in 94 of 9206 patients (1·0% [95% CI 0·8-1·3]; I2=0·0%).

在9206名患者中有94例治疗相关死亡（1.0% [95% 置信区间 0.8-1.3]; I2=0.0%）

The predominant causes were sepsis, pneumonia, neutropenic infection, respiratory failure, septic shock, and multi-organ failure.

主要死因包括败血症、肺炎、中性粒细胞减少性感染、呼吸衰竭、败血性休克和多器官衰竭。

interpretation

The toxicity profile of T cell-engaging bispecific antibodies varies substantially across cancer types and antibody classes.

T细胞双特异性抗体的毒性特征在不同癌症类型和抗体类别之间存在显著差异。

This meta-analysisprovides a comprehensive overview of treatment-related adverse eventincidenceand patterns, offering a valuable reference for optimising patient management in clinical practice.

这项荟萃分析提供了治疗相关不良事件发生率和模式的全面概述，为优化临床实践中患者管理提供了宝贵的参考。

funding

The National Natural Science Foundation of China and the Changsha Natural Science Foundation of Hunan Province of China.

中国国家自然科学基金和中国湖南省长沙市自然科学基金。