449 | BRIDGING TO CAR‐T CELL THERAPY IN LARGE B‐CELL LYMPHOMA WITH EITHER CONVENTIONAL THERAPY OR THE CD3xCD20 BISPECIFIC ANTIBODY GLOFITAMAB

J. K. Schleifenbaum, M. A. Neumann, N. Sieg, and R. Flümann equally contributing author. Introduction: Despite evidence for importance of remission prior CAR-T cell therapy in relapsed/ refractory large B-cell lymphoma (rrLBCL), no standardized bridging strategies exist to date. Due to favourable results in rrLBCL, the CD3/CD20 bispecific antibody glofitamab is a promising candidate for this purpose. While experimental data suggest synergistic effects of glofitamab with immunotherapy, its prolonged use may contribute to T-cell exhaustion. Consequently, we hypothesized that short-term glofitamab treatment before anti-CD19 CAR-T cell therapy achieves high response rates without compromising T-cell fitness. Methods: We conducted a retrospective sequential analysis comparing patients who received rapid ramp-up of glofitamab (GLO; October 2023-January 2025) with patients receiving non-glofitamab bridging (noGLO; September 2021-September 2023). Efficacy and tolerability were assessed using PET-CT (Deauville Score, DS; metabolic tumor volume, MTV) and occurrence of adverse events, respectively. Sequential sampling of biomaterial was performed to monitor levels of glofitamab, CAR-T cell expansion, and associated immune effects. Results: Besides GLO patients were older (median 64 vs. 54 years), clinical characteristics were comparable between GLO (n = 14) and noGLO (n = 23). The median number of prior treatment lines was two, the median time from start of bridging to CAR-T cell infusion was 39 days in both groups. Glofitamab was administered as monotherapy in 11/14 (79%) patients, three patients received simultaneous radiotherapy. NoGLO-treatment consisted of rituximab-based immunochemotherapy (12/23, 52%), tafasitamab-lenalidomide (6/23, 26%), high dose melphalan (3/23, 13%), or ibrutinib (2/23, 9%). The median MTV before bridging was 82 mL (2–1201 mL) in GLO and 222 mL (4–1127 mL) in noGLO. Treatment before CAR-T cell therapy led to remission in 9/14 (63%) of GLO- and 7/23 (30%) of noGLO-patients. The median MTV-reduction among responders was 98% (32%–100%) in GLO and 68% (51%–100%) in noGLO. Due to disease progression, one GLO-patient died before CAR-T cell infusion. Prior to CAR-T cell therapy, grade 3 or 4 cytopenia (anaemia, leuco- or thrombocytopenia) was observed in seven noGLO-patients (7/17, 42%) and in one GLO-patient (1/14, 7%). Neutropenic fever was reported in three noGLO-patients (3/17, 18%). Grade 1 or 2 CRS were seen in five GLO patients (5/14, 36%), with one also having an ICANS grade 2 and another developing an infection. Notably, no grade 3 or 4 CRS or ICANS occurred. Three months after CAR-T cell therapy, complete remission was achieved in 7/10 (70%) of GLO- and 8/22 (36%) of noGLO-patients. The progression-free survival after 90 days was 83% in GLO and 68% in noGLO. Conclusion: Despite small sample size and limited follow-up, our data suggest glofitamab as an effective and safe bridging prior to CAR-T cell therapy, potentially superior to conventional approaches. Data on molecular immune effects will be presented at the conference. Keywords: aggressive B-cell non-Hodgkin lymphoma; cellular therapies; combination therapies Potential sources of conflict of interest: C. Voltin Consultant or advisory role: Novartis Radiopharmaceuticals GmbH and Novartis Pharma GmbH P. J. Bröckelmann Consultant or advisory role: P.J.B. is an advisor or consultant for Hexal, Merck Sharp & Dohme, Need Inc, Stemline and Takeda Stock ownership: P.J.B. holds stock options in Need Inc Honoraria: P.