Abstract Introduction: Chimeric antigen receptor (CAR) T-cells have improved outcomes of patients (pts) with relapsed/refractory Non-Hodgkin Lymphoma (R/R NHL). However, 20% to 40% of those pts did not benefit from CAR-T therapies according to real-world study. Glofitamab, a CD20xCD3 bispecific antibody, was proven viable as salvage therapy following CAR-T treatment failure in the LYSA study, but its potential role as a CAR-T bridging therapy to improve patients' prognosis has yet to be investigated. Here we report the efficacy and safety of glofitamab bridging CAR-T therapies in pts with R/R NHL. Methods: Pts with R/R NHL who underwent leukapheresis received pre-treatment with obinutuzumab prior to the first dose of glofitamab. Based on disease progression status, pts received glofitamab monotherapy or glofitamab combined with gemcitabine + oxaliplatin/ BTK inhibitor/ methotrexate regimens prior to CAR-T infusion. Response rates are evaluated after bridging therapies and CAR-T therapies based on Lugano criteria. Adverse events were assessed according to American Society for Transplantation and Cellular Therapy consensus. Results: As of May 2025, 10 NHL pts who received glofitamab bridging CD19 CAR-T therapy in Wuhan Union Hospital were enrolled, among which 8 pts had a biopsy proven diffuse large B-cell lymphoma (DLBCL) whereas others had mantle cell lymphoma (n=1) and Burkitt lymphoma (n=1). The median age was 61.5 years (range: 20-79) and 70% of pts had Ann Arbor stage III/IV. Median lines of prior therapies was 2 (range: 2-5; ≥3 prior therapies: 60%) with two cases of autologous hematopoietic stem cell transplantation and 1 case of CAR-T therapy. All pts were refractory to their last line of therapy, including two with primary central nervous system lymphoma (PCNSL), two with secondary CNS involvement, one with bulky extramedullary disease (7 cm), and four harboring TP53 mutations. During glofitamab bridging therapy, grade 1 cytokine release syndrome (CRS) occurred in 4 pts and grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) in 1 patient. Viral infections developed in 4 pts. The overall response rate (ORR) was 66.7% (6/9 pts), with a complete metabolic response (CMR) rate of 22.2% (2/9 pts), excluding one patient unevaluable for response. The median interval between first glofitamab dose and CAR-T infusion was 31 (25-67) days. Seven pts (70%) experienced grade 1 CRS and 1 pts with PCNSL experienced grade 2 ICANS. Four pts experienced grade 3 infection. 100% pts responded to CAR-T therapies and 80% (8/10 pts) achieved CMR with PET-CT/PET-MRI at day+30 post-infusion. All subjects exhibited peripheral blood CAR-T expansion detectable via flow cytometry, reaching a median peak level of 13.57 CAR-T cells/μL (range: 3.2-403.4) at median peak time of day+11. CAR-T persistence (50 copies/μg DNA by ddPCR) was sustained in 80% pts at month 1. At a median follow-up of 6.0 months (range: 4-15.5), all pts remained treatment-free except one receiving regular glofitamab maintenance therapy. Disease relapse occurred in one patient at 3.5 months, while others were under active surveillance. Conclusion: Glofitamab bridging therapy prior to CAR-T demonstrated promising efficacy in pts with high-risk NHL, without significant safety concerns or detrimental impact on CAR-T cell kinetics. This study provides preliminary evidence for redefining therapeutic paradigms in non-Hodgkin lymphoma, particularly PCNSL, supporting further investigation through expanded validation cohorts and longitudinal outcomes assessment.
Zhang et al. (Mon,) studied this question.
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