Treatment-related adverse events of CD3-based T cell-engaging bispecific antibodies in patients with cancer: a meta-analysis of clinical trials
A partir d'une revue de la littérature (104 essais cliniques, 10 353 patients), cette méta-analyse évalue l'incidence des événements indésirables liés à l'utilisation d'anticorps bispécifiques engageant les lymphocytes T ciblant CD3 chez les patients atteints d'un cancer
Background: Clinical trials evaluating CD3-based T cell-engaging bispecific antibodies for cancer therapy have rapidly progressed from early investigations to clinical application. As these agents enter practice, it is essential to systematically characterise and summarise the range of treatment-related adverse events associated with these antibodies.
Methods: We conducted a meta-analysis by 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. The primary outcomes were the overall incidence of treatment-related adverse events, and toxicity profiles (ie, the incidence of each specified adverse event, for both all-grade and grade 3 or worse treatment-related adverse events). Pooled overall incidence and 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. Heterogeneity across studies was quantified with the I2 statistic. The study is registered at PROSPERO (CRD420251130333).
Findings: A total of 104 clinical trials enrolling 10 353 patients (7311 with haematological malignancies and 3042 with solid tumours) were included. For haematological malignancies, the overall incidence of 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. 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. 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]). 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. Treatment-related deaths occurred in 94 of 9206 patients (1·0% [95% CI 0·8–1·3]; I2=0·0%). The predominant causes were sepsis, pneumonia, neutropenic infection, respiratory failure, septic shock, and multi-organ failure.
Interpretation: The toxicity profile of T cell-engaging bispecific antibodies varies substantially across cancer types and antibody classes. This meta-analysis provides a comprehensive overview of treatment-related adverse event incidence and patterns, offering a valuable reference for optimising patient management in clinical practice.
The Lancet Oncology , résumé, 2026