In a meta-analysis reported in The Lancet Oncology, Zhu et al identified treatment-related adverse events associated with the use of CD3-based T-cell–engaging bispecific antibodies in patients with hematologic or solid cancers.
Study Details
The analysis included studies of CD3-based T-cell–engaging bispecific antibodies in patients with hematologic or solid cancers published through the end of July 2025. The primary outcome measures were overall incidence of treatment-related adverse events and grade 3 or worse events.
Key Findings
A total of 104 clinical trials with 10,353 patients were included in the analysis; of these patients, 7,311 had hematologic malignancies and 3,042 had solid tumors.
Among patients with hematologic malignancies, the overall incidence of all-grade treatment-related adverse events was 97.5% (95% confidence interval [CI] = 95.2%–98.7%; I² = 88.2%), with grade 3 or worse events occurring in 70.3% (95% CI = 62.6%–77.0%; I² = 94.4%).
Among patients with solid tumors, the overall incidence of any-grade treatment-related adverse events was 97.9% (95% CI = 95.7%–99.0%; I² = 57.0%), with grade 3 or worse adverse events occurring in 45.3% (95% CI = 38.4%–52.4%; I² = 87.0%).
Among patients with hematologic malignancies, the most common all-grade treatment-related adverse events were cytokine-release syndrome (43.3%), fever or pyrexia (31.1%), and anemia (22.8%). The most common grade 3 or worse events were neutropenia (18.1%), infections (12.3%), and anemia (12.0%).
Among patients with solid tumors, the most common all-grade treatment-related adverse events were cytokine-release syndrome (46.3%), fever or pyrexia (42.1%), and fatigue (32.2%). The most common grade 3 or worse events were increased γ-glutamyltransferase (3.7%), lymphopenia (3.5%), and fatigue (3.4%). Treatment-related death occurred in 94 patients overall (1.0%); predominant causes were sepsis, pneumonia, neutropenic infection, respiratory failure, septic shock, and multiorgan failure.
Among 18 distinct antibodies used across the studies, GPRC5D × CD3 constructs were associated with the highest rates of all-grade and grade 3 or worse treatment-related adverse events among patients with hematologic malignancies. Among patients with solid tumors, Gp100 × CD3 and survivin-derived peptide × CD3 constructs were associated with the highest rates of all-grade and grade 3 or worse events. For CD19 × CD3 antibodies and DLL3 × CD3 antibodies, the most common any-grade events were fever or pyrexia and cytokine-release syndrome; the most common grade 3 or higher events were neutropenia and decreased lymphocytes, respectively.
The investigators concluded: “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.”
Hong Zhu, MD, and Wei Liu, MD, of Xiangya Hospital, Central South University, Changsha, Hunan, China, are the corresponding authors for The Lancet Oncology article.
DISCLOSURE: The study was funded by the National Natural Science Foundation of China and the Changsha Natural Science Foundation of Hunan Province of China. For full disclosures of the study authors, visit thelancet.com.
