Abstract Background: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who fail bispecific antibody (BsAb) therapy face extremely poor clinical outcomes, 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 analyzed 11 consecutive R/R DLBCL patients who received CAR-T therapy after BsAb treatment failure at Beijing Tongren Hospital, Capital Medical University, from July 2023 to February 2025. The cohort had a median age of 55 years (range: 34–65) and a median of 5 prior lines of therapy (range: 2–8). All patients were refractory to BsAbs, with 90.9% (10/11) having ≥ 2 extranodal involvements and 27.3% (3/11) presenting with bulky disease. BsAb targets included CD3/CD20 (n = 9) and CD3/CD19 (n = 2), while CAR-T targets included CD19/CD22 dual-target (n = 9) and CD19 single-target (n = 2). The median washout period (from the last BsAb therapy to lymphapheresis for manufacturing autologous CAR-T cells) was 35 days (range 8–154). Primary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS); secondary endpoints included adverse event (AE) incidence. Results: With a median follow-up of 4.1 months (range: 1– 10.1), the best ORR was 100%, including complete response (CR) of 45.5% (5/11) and partial response (PR) of 54.5% (6/11). Median PFS and OS were not reached. Kaplan-Meier estimates for 6-month PFS and OS rates were 80.8% and 100%, respectively. Safety analysis revealed cytokine release syndrome (CRS) in 81.8% (9/11), all grade 1–2, and immune effector cell-associated neurotoxicity syndrome (ICANS) in 9.1% (1/11), with no grade ≥ 3 events. Hematologic toxicities included grade ≥ 3 neutropenia (100%, 11/11), thrombocytopenia (36.4%, 4/11), and anemia (36.4%, 4/11). CRS/ICANS were effectively managed with tocilizumab and corticosteroids, with no treatment-related deaths. Conclusion: CAR-T salvage therapy demonstrated remarkable efficacy (ORR 100%) and manageable safety in R/R DLBCL patients refractory to BsAbs, with dual-target (CD19/CD22) CAR-T potentially offering superior outcomes. Immature survival data suggested significant clinical benefit, though longer follow-up is needed to validate long-term efficacy. This study provided valuable evidence supporting CAR-T as an effective salvage strategy for BsAb-resistant patients. Keywords: diffuse large B-cell lymphoma; Bispecific antibodies; CAR-T cell therapy; salvage therapy; survival analysis Research funding declaration: This work was supported by grants from the National Natural Science Foundation of China (grant number: 82170181), Beijing Physician Scientist Training Project (grant number: BJPSTP-2024–01) to Liang Wang.
Jia Cong (2025) studied this question.