Efficacy and safety analysis of CAR-T cell salvage therapy in relapsed/refractory diffuse large B-cell lymphoma after failure of bispecific antibody treatment

Abstract Background Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who failed bispecific antibody (BsAb) therapy face an extremely poor prognosis, necessitating exploration of effective salvage strategies. This study aimed to evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in this population. Methods We retrospectively enrolled 12 consecutive R/R DLBCL patients who received CAR-T therapy after BsAb failure at Beijing Tongren Hospital, Capital Medical University, between July 2023 and February 2025.Clinical data were reviewed to evaluate efficacy and safety outcomes. Results The 12 patients (M: F = 6:6) had a median age of 53 years (range: 34–65), a median IPI of 3 (range: 1–5), and with a median of 5 prior lines of therapy (range: 1–8). The majority (91.7%, 11/12) had ≥ 2 extranodal sites, and 25% (3/12) had bulky disease (> 7.5 cm). Prior to CAR-T, 33.3% (4/12) were bispecific antibody-relapsed and 66.7% (8/12) were bispecific antibody-refractory. BsAb targets included CD3/CD20 (n = 9; commercial glofitamab n = 7, investigational n = 2) and CD3/CD19 (n = 3, investigational). CAR-T products were CD19/CD22 dual-target (n = 10) and CD19 single-target (n = 2). The median washout period from last BsAb to lymphapheresis was 42 days (range: 8–172).With a median follow-up of 9.3 months (range: 5.3–14), the best overall response rate was 100% (complete response 50%, partial response 50%).Median progression-free survival (PFS) and overall survival (OS) were not reached. The Kaplan-Meier estimates showed 12-month PFS and OS rates were 54.5% and 50.5%, respectively.Cytokine release syndrome occurred in 83.3% (all grade 1–2) and ICANS in 8.3%(all grade 1). Hematologic toxicities were frequent, with grade ≥ 3 neutropenia (100%), anemia (33.3%), and thrombocytopenia (33.3%). Non-hematologic toxicities included grade 1 AST/ALT elevations (33.3%) and coagulation abnormalities (elevated D-dimer 41.7%; grade ≥ 3 hypofibrinogenemia 16.7%). All adverse events were manageable with standard interventions, and no treatment-related deaths occurred. Conclusion CAR-T salvage therapy demonstrated high response rates and manageable safety in BsAb R/R DLBCL patients. Early survival data suggest promising clinical benefit in this high-risk population of BsAb-resistant patients, though extended follow-up is needed to confirm durability. This study provides supporting evidence for CAR-T as a potential salvage strategy in this setting.