Preliminary data on epcoritamab and glofitamab as bridging therapy prior to CAR T-cell treatment in Relapsed/Refractory large B cell lymphoma

Abstract Introduction: CAR T-cell therapies are currently approved as a second-line (2L) treatment for early relapsed or refractory large B-cell lymphoma (R/R LBCL). In France, due to a particularly long vein-to-vein time, most patients receive bridging therapy between leukapheresis and CAR T-cell infusion. In a recent study, bridging responses were evaluated in 514 patients intended to be treated with Axicabtagene Ciloleucel (Axi-cel) following various types of bridging therapy (mainly chemotherapy), with an overall response rate (ORR) of 44.9%, including 14.5% complete response (CR) and 29.9% partial response (PR). A good response to bridging was associated with better Axi-cel efficacy (Capes et al., ICML 2025). To date, the optimal bridging strategy remains a matter of debate, and no published data are available on the use of bispecific CD3xCD20 antibodies in this context. However, in pivotal trials bispecific in 3rd line (3L) achieve 60% ORR with improved overall survival (OS). These treatments are available in France as a 3L option for R/R LBCL. The aim of our study is to report real-world safety and efficacy data on the use of bispecific antibodies, Epcoritamab and Glofitamab, as bridging therapy prior to CAR T-cell infusion. Patients and Methods: We conducted a retrospective study using electronic medical records of patients over 18 years old with R/R LBCL who received bridging therapy with Glofitamab or Epcoritamab prior to CAR T-cell therapy at one center in Marseille and one center in Nice. Results: From September 2023 to April 2025, 17 patients treated with bispecifics as bridging before CAR T-cell therapy were identified (6 with Epcoritamab and 11 with Glofitamab). The median age at initiation of treatment was 68 years (range: 31–80), 11 patients (64.7%) were male, and 10 patients (58.8%) had primary refractory disease. Before bridging with bispecific antibodies, the median number of prior lines was two, and 15 patients (88.2%) were refractory to their last line of treatment. A total of 10 patients (58.8%) had advanced-stage disease (stage III–IV). Most patients received CAR T-cell therapy as second-line treatment (11 patients, 64%), with 3 as third-line (18%), 2 as fourth-line (12%), and 1 as fifth-line (6%). Bridging with Epcoritamab or Glofitamab was initiated as first-line bridging therapy in 6 patients (35%), or after failure of a first bridging strategy with chemotherapy in the remaining 11 patients (65%) who were treated with CAR T-cells as second-line therapy. Patients received 1 to 4 cycles of bispecific antibodies (median: 3 cycles). Regarding safety, 11 patients (64.7%) experienced grade 1–2 cytokine release syndrome (CRS), and 1 patient had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). No grade ≥3 adverse events were reported. Before CAR T-cell infusion, 7 patients (41.2%) achieved a complete response (3 with Epcoritamab and 4 with Glofitamab), 7 (41.2%) were in partial response (PR), and 3 (17.7%) had progressive disease (PD), 2 of whom died from progression before infusion. The median follow-up, calculated from the first cycle of bispecific antibodies, was 5.09 months. Among the 15 patients infused with CAR T-cell, 13 patients achieved CR, corresponding to 76% in the intention-to-treat (ITT) population and 87% in the per-protocol (PP) population. Among these patients who achieved CR, only one relapsed three months after CAR T-cell therapy; notably, this patient had progressive disease prior to infusion. The two patients who did not achieve a response after CAR T-cell therapy were in partial response before infusion. Conclusion: These preliminary data show that the use of Epcoritamab and Glofitamab as bridging therapy prior to CAR T-cell infusion appears to be safe and feasible, with acceptable toxicity and no grade ≥3 adverse events following bispecific antibody administration. In our cohort of 17 patients, more than 80% achieved a response before CAR T-cell infusion. Among the 15 patients who ultimately received CAR T-cells, 13 achieved a CR (87%).Although our median follow-up is still short and the patient cohort is small, these initial data suggest that bispecific antibodies have the potential to improve pre–CAR T-cell remission rates in patients with chemo-refractory disease. Updated results, including additional patients and post–CAR T-cell toxicity data, will be presented at the meeting.