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.

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2025
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