Glofitamab based combined therapy as bridging therapy before stem cell transplants and CAR-T therapy in large B-cell lymphoma. Free

Background:

Bispecific antibodies (bAbs) are increasingly used as bridging or maintenance therapy before chimeric antigen receptor T-cell (CAR-T) therapy, especially in patients resistant to the first bridging/maintenance regimen. However, the impact of this strategy on the safety and efficacy of CAR-T cells is unknown.

Objective:

This study aimed to investigate the safety and efficacy of glofitamab bridging therapy before stem cell transplants and CAR-T therapy in patients with large B-cell lymphoma.

Methods:

This single-center study evaluated glofitamab as bridging therapy prior to stem cell transplants and CAR-T cell infusion in relapsed/refractory large B-cell lymphoma patients. Eligible patients had histologically confirmed disease and were scheduled for CAR-T therapy. All patients received glofitamab as bridge therapy before stem-cell transplantation and CAR-T therapy. Patient characteristics including age, sex, disease stage, histologic subtype (DLBCL NOS, double/triple-hit lymphoma), and number of prior therapies were recorded. Treatment responses to glofitamab prior to CAR-T infusion were assessed using standard criteria (CR, PR, SD, PD). Following CAR-T therapy, responses were evaluated by PET-CT.Safety monitoring included assessment of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to established criteria. Progression-free survival (PFS) and overall survival (OS) were calculated from the time of CAR-T infusion.By comparing the CAR-T cell subpopulations before glofitamab treatment and before CAR-T cell infusion, we analyzed whether glofitamab had any impact on the preparation of CAR-T cells.Statistical analysis included descriptive statistics for baseline characteristics and response rates. Survival outcomes were analyzed using standard methods with median follow-up time calculated by reverse Kaplan-Meier estimation.

Results:

As of July 20, 2025, a total of 12 relapsed/refractory large B-cell lymphomas (6 women; median age at CAR-T infusion, 54 years [28-71 years]) were enrolled. All patients received glofitamab as CAR-T bridge therapy. Four patients had received more than two lines of therapy, 83% had stage III-IV disease, 67% had diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), and 17% and 8% had double-expression and double-hit or triple-hit lymphoma, respectively. 42% of patients had primary refractory disease, and 58% of patients had glofitamab combined with chemotherapy. Before stem cell transplants and CAR-T therapy, the efficacy of glofitamab was complete response (CR) in 3 patients (25%), partial response (PR) in 5 patients (42%), stable disease (SD) in 3 patients (25%), and progressive disease (PD) in 1 patient (8%). At the first post-PET-CT-based CAR-T review, 6 patients had a complete response (50%), 3 had a partial response (25%), and 2 had disease progression (17%), for an overall response rate of 75%. With a median follow-up of 9.6 months (95% confidence interval 4.022-15.178), the median progression-free survival (PFS) and overall survival (OS) were not reached. At 6-month, progression-free survival was 90%, and overall survival was 100%. In the safety-evaluable population (n=12), the most common adverse event (AE) was cytokine release syndrome ( Grade [Gr] 1,58%); no Gr ≥2 CRS events were reported and all events resolved. No immune effector cell-associated neurotoxicity syndrome events were reported. Infections occurred in 33% of pts. Neutropenia was the most common (58%). In total, no pt discontinued glofitamab treatment due to AEs. After glofitamab, 10 patients completed CART therapy. Six of 10 patients reported cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR-T therapy, including six CRS (five grade 1 CRS and one grade 2 CRS) and one grade 3 ICANS. In evaluable patients, there was no significant change in the functional assessment of effector T cells before and after glofitamab, indicating that the use of bispecific antibodies does not affect effector T cell function.

Conclusions: Glofitamab-based combination therapy has a high response rate as a bridge to stem cell transplantation and car-t therapy for large B-cell lymphoma. The safety was manageable and the treatment discontinuation rate was low. Updated data will be provided.