Glofitamab Plus CAR T-Cell Therapy Displays Real-World Safety, Efficacy in R/R B-Cell Lymphomas

The addition of the bispecific antibody glofitamab-gxbm (Columvi) to chimeric antigen receptor (CAR) T-cell therapy demonstrated safety and efficacy in the treatment of patients with relapsed/refractory B-cell lymphomas, according to data from a real-world study presented at the 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT).¹

The study included a cohort of patients who received glofitamab in combination with CAR T-cell therapy (n = 27) and an additional cohort treated with CAR T-cell therapy alone (n = 34). In the combination cohort, glofitamab was administered as bridging therapy and/or maintenance therapy around CAR T-cell therapy infusion.

Findings showed that patients treated with the bispecific antibody in combination with CAR T-cell therapy achieved an overall response rate (ORR) of 88.9%, including a complete response (CR) rate of 59.3% and a partial response (PR) rate of 26.0%. In patients who received CAR T-cell therapy alone, the ORR, CR, and PR rates were 67.6%, 44.1%, and 23.5%, respectively.

Notably, similar rates of patients in the bispecific arm (55.6%) and nonbispecific arm (56.0%) received CAR T-cell therapy plus autologous stem cell transplant. Additionally, no grade 3 or higher cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in patients treated with glofitamab plus CAR T-cell therapy. Grade 3 or higher CRS and ICANS occurred in 2.9% of patients each among patients treated with CAR T-cell therapy alone.

“[A] bispecific antibody [in] combination [with CAR T-cell therapy] delivered [improved] clinical outcomes and acts as an independent protective factor for progression-free survival,” presenting study author Jia Wei, MD, of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology in Wuhan, China, said in a presentation of the data.

What was the rationale for the real-world look at combining CAR T-cell therapy and a bispecific antibody in relapsed/refractory B-cell lymphomas?

Although CAR T-cell therapies have become key agents across B-cell lymphoma treatment paradigms, relapses driven by an immunosuppressive tumor microenvironment, antigen escape, and CAR T-cell exhaustion remain a challenge. Investigators hypothesized that combining glofitamab with a CAR T-cell product could lead to synergistic CAR T-cell persistence and prevent terminal differentiation.

In the United States, glofitamab received accelerated approval from the FDA in June 2023 for the treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after 2 or more lines of systemic therapy.²

To conduct the real-world study, investigators identified patients treated within the Department of Hematology at Tongji Hospital and Institute of Haematology and Blood Diseases Hospital (n =71).¹ Ultimately, 10 patients were excluded due to early death within 30 days of CAR T-cell therapy infusion (n = 2), missing follow-up data (n = 3), and co-infusion of more than 1 CAR T construct (n = 5).

In the study, patients treated with a bispecific antibody had a mean age of 54.0 years (range, 20.0-75.0) vs 48.5 years (range, 19.0-74.0) in the group that did not receive a bispecific antibody. Most patients in both groups had DLBCL (88.9%; 73.5%), and other histologies included Burkitt lymphoma (7.4%; 17.6%), mantle cell lymphoma (0%; 5.9%), high-grade B-cell lymphoma (0%; 2.9%), and primary mediastinal B-cell lymphoma (3.7%; 0%). Notably, 66.7% of patients in the bispecific antibody group had elevated LDH levels, vs 38.2% in the no-bispecific antibody group. Most patients had stage III or higher disease (88.9%; 70.6%).

Within the bispecific antibody group, 17 patients received glofitamab as bridging therapy, with treatment lasting for 2 cycles (n = 1), 3 cycles (n = 8), 4 cycles (n = 6), 6 cycles (n = 1), or 10 cycles (n = 1). Additionally, 18 patients received the bispecific antibody as maintenance, with treatment lasting for 1 cycle (n = 4), 2 cycles (n = 3), 3 cycles (n = 7), 4 cycles (n = 1), 7 cycles (n = 1), and 12 cycles (n = 1).

Regarding CAR T-cell therapy administration, 37.0% of patients in the bispecific antibody group received CD19-directed therapy, 3.7% received CD19/20-directed therapy, and 59.3% received CD19/22-directed therapy. These rates were 0%, 53.0%, and 47.0%, respectively, in the no-bispecific antibody group.

Disclosures: Wei reported no financial conflicts of interest.

References

1. Yang X, Wang Y, Fang Y, et al. Real-world evidence for the safety and efficacy of glofitamab combined with CAR-T therapy in relapsed/refractory B-cell lymphoma. Abstract presented at: 52nd EBMT Annual Meeting; March 22-25, 2026; Madrid, Spain. Abstract OS13-01.
2. Columvi. Prescribing information. Genentech, Inc; 2025. Accessed March 24, 2026. https://www.gene.com/download/pdf/columvi_prescribing.pdf