CD20×CD3 Bispecific Antibodies May Be Feasible Bridging Strategy in LBCL

CD20×CD3 bispecific antibodies displayed feasibility as an effective bridging strategy prior to CAR T-cell therapy among patients with large B-cell lymphoma (LBCL), according to findings from a comprehensive analysis presented at the European Hematology Association (EHA) 2026 Congress.

Among patients treated with bispecifics for their bridging therapy (BisCAR; n = 67) or conventional bridging therapy (ConCAR; n = 45), cytopenias occurred at a similar rate between groups, although events were largely higher grade in the ConCAR group. The total incidence of cytopenia was 24% vs 33% in the respective groups, and 3% vs 22% experienced grade 3 to 4 cytopenia.

Additionally, cytokine release syndrome (CRS) occurred in 52% of patients in the BisCAR arm, of which 4% were grade 3 or 4. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed at a rate of 4% in the BisCAR arm, which were exclusively grade 1 or 2. Study presenter Ruth Fluemann expressed that bispecifics were well tolerated as bridging therapy.

Moreover, safety outcomes post-CAR T treatment were not significantly impacted by the type of bridging therapy used. The overall incidence of CRS was 72% vs 74% in the BisCAR and ConCAR arms, respectively, with 2% vs 7% experiencing grade 3 or 4 events. Any-grade ICANS occurred at a rate of 26% vs 29%, with 4% vs 13% of each arm experiencing grade 3 or 4 events.

Furthermore, response rates favored the bispecific vs the conventional arm. The objective response rate (ORR) in the BisCAR arm was 69% (95% CI, 56%-79%) vs 61% (95% CI, 44%-76%) in the ConCAR arm for the duration of bridging therapy. The respective rates at 1 month into CAR T-cell treatment were 85% (95% CI, 74%-92%) vs 72% (95% CI, 56%-85%); at 3 months into CAR T-cell treatment, the rates were 80% (95% CI, 67%-89%) vs 66% (95% CI, 50%-80%).

The addition of gemcitabine and oxaliplatin (GemOx) to glofitamab-gxbm (Columvi) conferred deep remissions more rapidly than bispecific monotherapy, with an ORR of 75% (95% CI, 53%-90%) vs 65% (95% CI, 49%-79%) during bridging therapy. Notably, the glofitamab/GemOx combination elicited a complete response (CR) rate of 42% during the bridging therapy period. The respective rates at 1 and 3 months into CAR T treatment were 83% (95% CI, 63%-95%) vs 85% (95% CI, 71%-94%) and 73% (95% CI, 50%-89%) vs 81% (95% CI, 65%-92%).

“We did not see any evidence for a compromise of CAR T-cell efficacy by bispecific antibody exposure,” Fluemann noted in the presentation. “Also, when we performed multivariable analysis, bridging strategy was not associated with inferior progression-free survival [PFS] or overall survival [OS].”

Fluemann is from Department I of Internal Medicine of the Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf at University of Cologne and Medical Faculty and University Hospital Cologne in Cologne, Germany; the Cologne Lymphoma Working Group in Cologne, Germany; and the Institute for Molecular Immunology at the University of Cologne in Cologne, Germany.

The study was a multicenter retrospective analysis of 112 patients across 9 German centers. A total of 67 patients represented the BisCAR arm and received glofitamab alone or with GemOX or epcoritamab-bysp (Epkinly). In the ConCAR arm, 45 patients received traditional bridging therapy or none at all. In the BisCAR arm, most patients received glofitamab alone (52%) or with GemOx (36%). For the ConCAR arm, the most common bridging strategy was polatuzumab vedotin-piiq (Polivy) plus bendamustine and rituximab (Rituxan; 29%), and 20% of patients received no bridging therapy.

The study evaluated safety, response, and PFS and OS outcomes. Additionally, immune profiling before and after CAR T-cell treatment was assessed.

The median age in the BisCAR and ConCAR arms was 66 years (range, 25-85) vs 60 years (range, 24-84). Most patients in each arm were male (58% vs 67%) and had primary LBCL (94% vs 77.8%). A total of 52% vs 38% had a Germinal Center B-cell (GCB) cell-of-origin, 61% vs 36% received lisocabtagene maraleucel (Breyanzi), and 24% vs 13% had a high International Prognostic Index (IPI) score, defined as 4 or 5. The median number of lines prior to intent to administer CAR T were 2 (range, 0-6) and 2 (range, 1-5) in each of the respective arms.

Disclosure: Fluemann noted receiving a travel grant from Avanzanite.

Reference

Neumann MA-C, Zieger HK, Flümann R, et al. Comprehensive analysis of bridging to CAR T-Cell therapy in large B-cell lymphoma with conventional treatment or CD3×CD20 bispecific antibodies. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S241.