Efficacy and safety of bridging versus non-bridging chimeric antigen receptor t-cell therapy in relapsed/refractory diffuse large b-cell lymphoma : A systematic review and meta-analysis

Abstract Introduction:Chimeric antigen receptor T-cell (CART) therapy has become the standard of care for patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL). However, durable responses are achieved only in about 30%-40% of patients, likely due to suboptimal disease control during the CART manufacturing period. Bridging therapy (BT) refers to anticancer management during this time frame. Currently, the lack of standardized guidelines on BT has led to considerable variability in clinical practice. Our paper aims to address the effect of bridging strategies on outcomes of CART Therapy. Methodology:We conducted a systematic search of PubMed, Embase, and Cochrane databases to identify studies, comparing BT and non BT in r/r DLBCL patients treated with CAR-T cell therapy until july 2025. The primary outcomes of this analysis are 1-year progression-free survival (PFS) and overall survival (OS). The secondary outcomes consist of grade 3 cytokine release syndrome (CRS) and neurotoxicity. Risk ratios (RR) with 95% confidence intervals (CIs) were used to calculate the dichotomous outcomes using R version 4.4.2 with a random-effects model for all outcomes. Results:A total of 4 studies consisting of 1149 patients undergoing CART cell infusion were included in the study. The BTs evaluated were radiotherapy (RT), chemotherapy (CT) and combined modality therapy (RT + CT). PFS did not significantly between BT and No BT groups, CT with a RR of 0.77 95% CI: 0.55 - 1.07(p=0.12), while RT and RT + CT showed RR of 1.01 95% CI: 0.65 - 1.56(p=0.97) and 0.95 95% CI: 0.63 - 1.43(p=0.80) respectively. BT had a favourable OS with CT (0.74 95% CI: 0.64 - 0.86; p0.001), while RT (0.97 95% CI: 0.83 - 1.13(p=0.97)) and RT + CT (0.75 95% CI: 0.54 - 1.03(p=0.07)) did not show statistically significant benefit. BT showed no significant increase in adverse event profile consisting of grade 3, CRS and neurotoxicity. CRS rates were comparable among subgroups (CT showing RR of 1.32 95% CI: 0.52 - 3.34(p=0.55), RT 1.12 95% CI: 0.42-2.99(p=0.82) and RT + CT 3.76 95% CI: 1.11 - 12.75(p=0.034). Neurotoxicity was similar across all modalities (CT 1.18 95% CI: 0.63 - 2.21;p=0.60, RT 1.16 95% CI: 0.66 - 2.03;p=0.60, CT + RT 0.66 95% CI: 0.21 - 2.09;p=0.47). Conclusion:Bridging therapy did not provide a consistent benefit in view of survival and safety outcomes when compared to bridging, however bridging CT demonstrated better OS without increase in adverse events. This study is limited by lack of patient specific data. To define the true advantage and optimal approach to bridging strategies, further studies incorporating patient specific data and tumor burden, are warranted.