Impact of Bridging Response on Outcomes after CD19 CAR T-Cell Therapy in Large B-Cell Lymphoma

Abstract

Bridging therapy (BT) is frequently administered during CD19 CAR T-cell manufacturing for relapsed or refractory large B-cell lymphoma (LBCL), and although disease status at infusion has been associated with outcomes, the prognostic relevance of response to BT, independent of BT modality, has been variably defined in real-world cohorts. To assess the impact of bridging response on clinical outcomes after CD19 CAR T-cell therapy in patients with LBCL, and to determine whether response to BT or BT regimen type are associated with progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. We conducted a retrospective multicenter study of 377 adults with relapsed/refractory LBCL treated with commercial CD19 CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) between 2020 and 2024. BT was administered in 248 patients (66%) during the manufacturing period and categorized by regimen type. Response to BT and CAR T therapy were assessed using Lugano criteria. The primary endpoints were PFS and OS after CAR T infusion. Secondary endpoints included rates of cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and hematologic toxicity. Multivariable Cox regression models adjusted for performance status, lactate dehydrogenase (LDH), CAR T product, and BT category were applied to evaluate associations. Among patients receiving BT, the overall response rate prior to CAR T infusion was 49%, including complete response (CR) in 12%. Patients achieving CR or partial response (PR) to BT had significantly longer PFS and OS compared with those with stable or progressive disease (SD/PD) (median PFS and OS not reached vs shorter durations; P < .01). In multivariable analysis, response to BT remained an independent predictor of both PFS (hazard ratio [HR] for SD/PD versus CR: 2.59, 95% confidence interval [CI] 1.28 to 5.22) and OS (HR: 4.53, 95% CI 1.64 to 12.5), while BT modality itself was not independently associated with survival outcomes. Patients with favorable BT responses demonstrated lower pre-infusion tumor burden and reduced systemic inflammatory markers. Rates of CRS and ICANS did not differ significantly by BT response category. Severe hematologic toxicity was more frequent following intensive chemotherapy-based BT regimens but was not independently associated with long-term outcomes. In this large observational real-world multicenter cohort, response to BT, rather than the specific BT modality, was strongly associated with improved survival outcomes after CD19 CAR T-cell therapy in LBCL. These findings emphasize the prognostic significance of pre-infusion disease control and support treatment strategies focused on achieving effective BT responses while balancing regimen toxicity.