Safety of glucagon-like peptide-1 receptor agonists in patients receiving chimeric antigen receptor T cell or bispecific T cell engager therapy.

Abstract

e24016 Background: Chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BiTE) therapies are associated with significant toxicities, including cytokine release syndrome (CRS), infections, and cardiometabolic complications. GLP-1 receptor agonists (GLP-1RAs) have immunometabolic effects that may theoretically influence inflammatory toxicities during T-cell–redirecting therapies; however, their safety in patients undergoing CAR-T or BiTE therapy remains poorly defined. Methods: We conducted a retrospective, multicenter cohort study using the TriNetX database, including adults (≥18 years) with hematologic malignancies receiving FDA-approved CAR-T/BiTE therapy. Patients were stratified by GLP-1RA exposure (between 1 month and 1 year of CAR-T/BiTE therapy) and compared with GLP-1RA-naïve controls. Cohorts were propensity score matched 1:1 for age, sex, malignancy type, and baseline comorbidities (heart failure, diabetes, prior myocardial infarction). Primary outcome was 1-year all-cause mortality as a global safety endpoint, and secondary outcomes were CRS, tocilizumab use, and C-reactive protein (CRP) levels. Cohort comparisons were performed using built-in TriNetX statistical methods, with regression-based estimates reported as odds ratios (ORs) and time-to-event analyses using Cox proportional hazards models. Results: Among patients receiving CAR-T/BiTE therapy, 141 with prior GLP-1RA exposure were identified and propensity score–matched to GLP-1RA–naïve controls. No significant difference in mortality was observed between groups (OR 1.29, 95% CI 0.76–2.20). Similarly, GLP-1RA exposure was not associated with differences in CRP levels (p = 0.26), tocilizumab utilization (OR 0.79, 95% CI 0.47–1.35), or incidence of CRS (OR 1.49, 95% CI 0.68–3.26). Conclusions: GLP-1RA use was not associated with increased toxicity, inflammatory complications, or mortality in patients undergoing CAR-T or BiTE therapy, supporting the short-term clinical safety of GLP-1RA exposure in this high-risk population.