Impact of mRNA SARS-CoV-2 vaccination on CAR T-cell therapy outcomes in hematologic malignancies: A multi-center real-world analysis.

11001 Background: The clinical landscape of hematologic malignancies has been reshaped by Chimeric Antigen Receptor (CAR) T-cell therapies; however, their administration is intrinsically associated with immune-mediated toxicities, specifically cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). The interaction between the immunogenic stimulus of mRNA SARS-CoV-2 vaccines and the systemic inflammatory milieu of CAR T-cell therapy remains undefined in real-world practice. This study aimed to delineate the impact of mRNA vaccination on survival outcomes and immunotoxicity profiles within this vulnerable patient population. Methods: We conducted a retrospective cohort study using the TriNetX global federated health research network. We identified patients with hematologic malignancies who received CAR T-cell therapy using ICD-10 and RXNORM codes. Patients were stratified into two cohorts based on whether they received mRNA-based SARS-CoV-2 vaccines. The cohorts were 1:1 propensity score-matched for age, sex, race, staging, and comorbidities. The primary outcome was all-cause mortality at 3 years, assessed with Hazard Ratios (HR). Secondary outcomes included CRS grade 1/2 and 3/4, and ICANS, both graded per the ASTCT criteria, and assessed with Odds Ratios (OR). Results: A total of 3,199 CAR T-cell patients (222 mRNA vaccine recipients and 2,977 without the mRNA vaccine) were identified. After 1:1 propensity score matching, 218 patients remained in each cohort. The 3-year mortality was significantly lower among mRNA SARS-CoV-2 vaccine recipients as compared to non-recipients (HR 0.608; 95% CI, 0.411 - 0.901). The mRNA vaccine group had a higher rate of CRS 1/2 (OR 1.577; 95% CI, 1.056 - 2.356). However, there were not enough cases of CRS 3/4 to compare the two cohorts. Furthermore, there was no significant difference in ICANS between the two cohorts (OR 0.8262; 95% CI, 0.522–1.37). Conclusions: In this propensity score-matched analysis of real-world data, mRNA SARS-CoV-2 vaccination was associated with a significantly superior long-term survival among CAR T-cell recipients. These findings build on early pre-clinical data related to SARS-CoV-2 mRNA vaccines demonstrating substantial increase in type I interferon, enabling innate immune cells to prime CD8 + T cells. The results provide early real-world clinical evidence and pave the way for prospective validation. Key outcomes in CAR T-cell recipients. Outcome Effect of mRNA Vaccination (95% CI) p Value All-cause mortality (3-year) HR 0.61 (0.41–0.90) 0.01 CRS grade 1/2 OR 1.58 (1.06–2.36) 0.03 ICANS (any grade) OR 0.83 (0.52–1.37) 0.41