Int J Immunopathol Pharmacol. 2026 Jan-Dec;40:3946320261499210. doi: 10.1177/03946320261499210. Epub 2026 Oct 27.
ABSTRACT
BackgroundT-cell-engaging bispecific agents and related T-cell-engaging therapies are increasingly used across hematologic malignancies and selected solid tumors. Infection is a clinically important safety concern, but infection-focused post-marketing comparisons across the current product set remain limited. We evaluated infection-related adverse event reporting for T-cell-engaging agents using the FDA Adverse Event Reporting System/Adverse Event Monitoring System (FAERS/AEMS).MethodsPublic FAERS/AEMS quarterly ASCII files from 2022Q1 to 2026Q1 were analyzed. Reports were deduplicated by retaining the latest case version for each CASEID, and exposure was defined as a target T-cell-engaging agent recorded as the primary suspect drug. Infection-related events were identified with a prespecified MedDRA preferred-term dictionary and were summarized using a structured dominant-category framework. Disproportionality was assessed using reporting odds ratio (ROR) with 95% confidence interval (CI), with proportional reporting ratio (PRR) and information component (IC) as supportive metrics. Reporting followed the READUS-PV guideline for disproportionality analyses of individual case safety reports.ResultsAmong 6,102,203 deduplicated primary-suspect reports, 15,108 involved a target T-cell-engaging agent, of which 3,114 were infection-related (20.6%). The class-level infection-related reporting signal was significant (ROR 2.03 (1.95-2.11); IC025 0.80). The largest number of infection-related reports was observed for Teclistamab (Tecvayli) (829 reports), whereas the highest drug-level ROR was observed for Elranatamab (Elrexfio) (ROR 4.38 (3.94-4.87)). Prominent preferred-term signals included pneumonia (ROR 2.01 (1.84-2.21)), sepsis (ROR 3.76 (3.32-4.24)), septic shock (ROR 4.39 (3.71-5.19)), cytomegalovirus infection reactivation (ROR 27.19 (23.39-31.60)), and cytomegalovirus infection (ROR 12.60 (10.71-14.82)). The class-level signal persisted under the narrower infection definition (2,545 reports; ROR 1.95, 95% CI 1.87-2.03). Concordant DailyMed infection terms and FAERS/AEMS infection signals were found for 7 agents.ConclusionsFAERS/AEMS data showed a class-level reporting signal for infection-related adverse events with T-cell-engaging agents, particularly among BCMA x CD3 and CD20 x CD3 therapies. Cytomegalovirus-related events, pneumonia, and sepsis were prominent signal patterns. These findings are hypothesis-generating reporting patterns and should not be interpreted as incidence estimates, relative risks, or proof of causality.
PMID:42947501 | DOI:10.1177/03946320261499210