Cardiovascular outcomes after bispecific T-cell-engager therapy in multiple myeloma: A propensity-matched real-world study.

Abstract

e24007 Background: Bispecific T-cell engager (BiTE) therapies have emerged as highly effective immunotherapeutic agents for relapsed and refractory multiple myeloma by redirecting cytotoxic T-cell activity toward malignant plasma cells. However, immune activation associated with BiTE therapy may lead to systemic inflammation, cytokine release, and off-target effects, potentially increasing cardiovascular complications and healthcare utilization. Real-world evidence describing cardiovascular outcomes and longitudinal healthcare burden in this population remains limited. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, a federated electronic health record platform encompassing 70 healthcare organizations. Adult patients with multiple myeloma treated with BiTE agents (elranatamab, talquetamab, teclistamab, or linvoseltamab) were compared with BiTE-naïve multiple myeloma controls. The index date was defined as the first BiTE administration. Outcomes were assessed at 6 months and 1 year. Primary outcomes included all-cause mortality and emergency department (ED) visits or hospital admissions. Secondary outcomes included heart failure exacerbations, venous thromboembolism, major adverse cardiovascular events (MACE), and selected cardiovascular endpoints. Propensity score matching (1:1) was performed using demographic, clinical, procedural, medication, and laboratory variables. Time-to-event analyses utilized Kaplan–Meier methods and Cox proportional hazards models. Results: After matching, 843 BiTE-treated patients were compared with 843 non-BiTE controls with excellent covariate balance. At 6 months, mortality was numerically higher in the BiTE group but not statistically significant (15.8% vs 13.9%; hazard ratio [HR] 1.22; p=0.286). BiTE therapy was associated with significantly increased ED visits or hospital admissions (58.1% vs 37.7%; HR 2.00; p<0.001) and higher heart failure exacerbations (17.9% vs 11.9%; HR 1.63; p<0.001). No significant differences were observed in venous thromboembolism or MACE. At 1 year, excess ED visits or hospital admissions (63.3% vs 45.2%; HR 1.98; p<0.001) and heart failure exacerbations (19.6% vs 14.0%; HR 1.58; p<0.001) persisted. Mortality showed a nonsignificant trend toward higher risk in the BiTE group (20.3% vs 19.0%; HR 1.24; p=0.054). Conclusions: In this large real-world cohort, BiTE therapy in multiple myeloma was associated with increased healthcare utilization and heart failure exacerbations without a statistically significant increase in mortality or thrombotic events. These findings emphasize the need for cardiovascular risk surveillance and multidisciplinary management in patients receiving BiTE therapies.