Accelerated Glofitamab as Urgent Bridging to CAR T-Cell Therapy in High-Risk Relapsed/Refractory Large B-Cell...

Conventional glofitamab step-up dosing reaches the 30-mg target dose approximately 3 weeks after obinutuzumab. This interval may be difficult to accommodate in patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who require disease control within days before cellular therapy. We retrospectively evaluated an accelerated bridging schedule of obinutuzumab 1000 mg on day 1 followed by glofitamab 2.5 mg on day 4, 10 mg on day 8, and 30 mg on day 11. Forty-one consecutive adults with R/R LBCL were included. All patients had a documented plan to proceed to chimeric antigen receptor (CAR) T-cell therapy after glofitamab initiation. The cohort was high risk: 90.2% had stage III-IV disease, 70.7% had an International Prognostic Index score of 3%-5%, and 46.3% had central nervous system (CNS) involvement. Cytokine release syndrome (CRS) occurred in 8 patients (19.5%), including 1 grade 3 event; immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients (4.9%), both grade 1-2. At the prespecified day-12 assessment, the overall response rate was 80.5% (33/41). Among 19 patients with CNS involvement, 18 (94.7%) responded, and cerebrospinal fluid cytology cleared in all evaluable patients with baseline positivity. After one cycle, 38 of 41 patients (92.7%) proceeded to planned CAR T-cell therapy. In this relatively small retrospective cohort, accelerated glofitamab bridging therapy showed rapid early antitumor activity and manageable toxicity, and a high response rate after subsequent CAR T-cell therapy. Longer-term outcomes could not be attributed to glofitamab alone. These findings are descriptive and require prospective validation.