Short-course glofitamab enables effective bridging to CAR-t therapy in B-NHL

Abstract Background: High tumor burden is associated with poor outcomes in CAR-T cell therapy. Although radiotherapy and chemotherapy are commonly used as bridging strategies, some patients fail to achieve adequate disease control. Short-course bispecific antibody (BsAb) therapy prior to CAR-T may serve as an alternative cytoreductive approach. Glofitamab, a CD20×CD3 BsAb, has shown promising activity in relapsed/refractory large B-cell lymphoma (LBCL), and may help secure a therapeutic window before CAR-T infusion. Methods: We retrospectively analyzed 9 patients with LBCL who received glofitamab as bridging therapy before CAR-T treatment at Beijing Gobroad Hospital between January 2024 and May 2025. Histologic subtypes included: diffuse large B-cell lymphoma (DLBCL, n=5), Burkitt lymphoma (n=2), mantle cell lymphoma (n=1), and high-grade B-cell lymphoma (n=1). Median age was 41 years (range, 24–75), and 89% were male. ECOG ≥2 was noted in 2 patients (22%), IPI ≥3 in 6 (67%), and bulky disease (≥7.5 cm) in 5 (56%). Most patients (78%) had received ≥3 prior lines of therapy; 2 had undergone autologous stem cell transplantation, and 5 had relapsed after previous CAR-T therapy. All patients underwent leukapheresis for CAR-T manufacturing before receiving glofitamab. OS was defined from first glofitamab use to death from any cause; PFS was defined from first glofitamab to progression or death. Results: Prior to glofitamab, 7 patients had progressive disease (PD) and 2 had partial response (PR). The median number of glofitamab cycles was 2 (range, 1–9). After the first cycle, the overall response rate (ORR) was 100% (9/9), with 2 complete responses (CR, 22%). Five patients developed grade 1 cytokine release syndrome (CRS); no ICANS was observed.In the second cycle (n=7), ORR remained 100%, with 1 CR (14%) and no CRS/ICANS.Third cycle (n=3): ORR was 100% with a CR rate of 33%. Disease progression occurred in two patients during cycles 6 and 9, respectively. Median time from glofitamab to second CAR-T infusion was 208 days (range, 33–307).At the time of CAR-T infusion, disease status was CR in 3, PR in 4, and PD in 2.At 3 months post-CAR-T, 7 patients were evaluable: 5 remained in remission. Among 5 patients who had failed prior CAR-T therapy, 3 achieved CR after glofitamab bridging and second CAR-T, yielding an ORR of 60%. Post-CAR-T CRS occurred in 7/9 patients (78%), all grade 1–2, with no ICANS reported.No cases of prolonged cytopenia or infection-related mortality were observed. After a median follow-up of 8.75 months, median OS and PFS were 12.46 and 5.92 months, respectively. Outcomes were similar in the subgroup of patients who underwent a second CAR-T infusion. Conclusion: Short-course CD20×CD3 BsAb therapy with glofitamab as a bridging and cytoreductive strategy before CAR-T infusion may reduce tumor burden and improve treatment feasibility in B-NHL. Further prospective validation is warranted.