The impact of COVID-19 mRNA vaccination on bispecific antibody outcomes in hematologic malignancies: A retrospective multicenter cohort study.

7040 Background: Bispecific antibody (BsAb) therapies are universally available, off-the-shelf therapies and are increasingly being used in hematologic malignancies. However, long term efficacy, durability and survival data are lacking. Furthermore, widespread expansion is limited by immune-mediated toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. The real-world impact of mRNA SARS-CoV-2 vaccines on outcomes in patients receiving BsAb therapies remain unknown. Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX federated electronic health record network. Adult patients with hematologic malignancies who received BsAb therapy were included and stratified by receipt of mRNA SARS-CoV-2 vaccines. Patients with documented COVID-19 infection or post-COVID-19 conditions were excluded. Cohorts were matched 1:1 on baseline demographic and clinical characteristics, yielding 238 patients per group, and followed longitudinally. Outcomes included all-cause mortality, any-grade CRS grade, and ICANS, graded per the ASTCT criteria. Associations were assessed using risk estimates and time-to-event analyses with Kaplan-Meier methods and Cox proportional hazards models. Event burden was evaluated by the number of events per patient among those experiencing CRS or ICANS. Results: All-cause mortality was lower in the vaccinated cohort compared with the unvaccinated cohort (21.4% vs 29.0%; p=0.057), with significantly improved survival on time-to-event analysis (hazard ratio [HR] 0.55; 95% CI, 0.38-0.79; log-rank p=0.001). The incidence of CRS grade 1/2 was similar between cohorts (25.2% vs 24.0%), with no difference in time to first CRS event (HR 0.98; 95% CI, 0.68-1.41). ICANS incidence was also comparable (10.9% vs 11.3%), with no significant difference in time-to-event (HR 0.87; 95% CI, 0.51-1.50). Among patients who developed ICANS, the vaccinated cohort experienced a higher mean number of ICANS episodes (2.58 vs 1.67; p=0.036) see (table1). Conclusions: In this propensity score-matched real-world analysis, mRNA SARS-CoV-2 vaccination was associated with significantly reduced all-cause mortality (HR, 0.55) among patients receiving BsAb therapy, without an increased risk of CRS grade 1/2 or ICANS. These findings support the safety of mRNA vaccination in this high-risk population and suggest a potential survival benefit necessitating prospective validation. Outcome Vaccinated (n=238) Unvaccinated (n=238) Key Effect All-cause mortality 21.4% 29.0% HR 0.55 (95% CI 0.38-0.79) CRS grade 1/2 25.2% 24.0% HR 0.98 (95% CI 0.68-1.41) CRS grade 1/2 episodes (mean) 2.98 2.35 P=0.16 ICANS 10.9% 11.3% HR 0.87 (95% CI 0.51-1.50) ICANS episodes (mean) 2.58 1.67 p=0.036