Purpose: We aimed to analyze the safety and efficacy of a radiation bridging regimen with or without chemotherapy compared with chemotherapy alone prior to CAR T-cell treatment for relapsed/refractory aggressive B-cell lymphoma (r/r ABL).Methods and materials: In this study, 45 out of 105 patients enrolled in CD19/22 CAR T-cell "cocktail" clin-ical trial were excluded, including 34 patients without bridging treatment. Total 60 patients receiving CAR T-cell therapies with bridging regimens as chemotherapy alone (C-CAR-T group, n = 31), and radio-therapy with or without chemotherapy (R-CAR-T group, n = 29) between February 2017 and October 2020 were retrospectively analyzed.Results: No significant toxicities were identified in the R-CAR-T group, and no patients in either group experienced CAR-T-related deaths. However, the R-CAR-T group showed a lower incidence of cytokine release syndrome (CRS) of grade >= 3 relative to the C-CAR-T group (0% vs 19.4%, P = 0.036). The incidence of neurological toxicity was 9.9% and 6.9% in the C-CAR-T group and R-CAR-T group, respectively (P = 0.697). The R-CAR-T group achieved a higher overall response rate (ORR) at the day 30 assessment (82.8% vs 45.2%, P = 0.0025). Further analyzing the outcomes, the R-CAR-T group presented a better 1 -year progression-free survival (PFS) rate than the C-CAR-T group (46.9% vs 22.6%, P = 0.0356). Intriguingly, the bridging radiation regimen extremely improved the 6-month PFS (50.8% vs 16. 7%, P = 0.0369) and 1-year overall survival (OS) (56.3% vs 33.3%, P = 0.0236) rates in patients with bulky dis-ease. The study also found that conducting radiotherapy as a bridging regimen was an independent factor that predicted better PFS (HR: 0.534, 95% CI: 0.289-0.987, P = 0.045).Conclusions: Our results provide and strengthen novel insights that the use of radiotherapy as a bridging strategy was demonstrated to reduce the incidence of severe CRS and improve the PFS of patients. In sub-group analysis, it was confirmed that radiotherapy can improve PFS and OS in patients with bulky dis-ease. These findings open new avenues to improve the efficacy and safety of CAR T-cell therapy.(c) 2022 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 177 (2022) 53-60