Case Studies Focus on Glofitamab as Bridge to CAR T in MCL

Whether to use bispecific antibodies before or after chimeric antigen receptor (CAR) T-cell therapy has been a topic of much discussion among clinicians who treat patients with different blood cancers. In most cases, the preference is CAR T first, then bispecifics.

But for every rule, there are exceptions.

If a bispecific is being given first as part of strategy, that’s something else entirely. And that was the case with a small group of patients with mantle cell lymphoma (MCL) treated with glofitamab (Columvi; Roche) as a bridging therapy ahead of CAR T-cell therapy.

Glofitamab, a T-cell-engager, works by simultaneously binding to CD20 on cancer cells and CD3 on T-cells, bringing the body's immune cells directly to the tumor to destroy it. And the 3 patients pretreated with the bispecific prior to receiving CAR T responded fairly well, despite heavy pretreatment; their results were part described in a short report in eJHaem.¹

The patients receiving glofitamab as pretreatment patients were part of a group of 10 male patients treated with the bispecific between January 2023 and May 2024. The authors stated that prior to European Medicines Agency approval of the therapy for diffuse large B-cell lymphoma (DLBCL), glofitamab was administered through a compassionate use program; afterward, patients received glofitamab as off-label therapy following an informed consent process.^1,2

All 10 patients treated at 5 sites in Austria and Italy were male, median age 65, and heavily pretreated (median 4.5 prior lines), with 70% high-risk secondary MIPI and 50% prior CAR T-cell exposure. Three of the 10 patients received glofitamab explicitly as bridging therapy before CAR T-cell infusion with brexucabtagene autoleucel (brexu-cel/Tecartus; Kite/Gilead) in MCL.¹

To avoid T-cell dysfunction from prior T-cell-redirecting therapy, leukapheresis for CAR T manufacturing was performed before glofitamab was started. After a median of just 2 cycles (range 2–6) of glofitamab, all 3 bridging patients successfully proceeded to brexu-cel infusion, with pre-CAR T responses of 1 complete response (CR), 1 partial response (PR), and 1 mixed response. Notably, all 3 achieved CR by 2 months following CAR T-cell therapy and remained in CR at a median follow-up of 12.2 months.

Across the full cohort of 10 patients, cytokine release syndrome (CRS) occurred in 7/10 patients; mostly grade 1–2. Tocilizumab was used in 5 patients, including 2 patients with grade 3 CRS who fully recovered. Immune Effector Cell-Associated Neurotoxicity Syndrome occurred in 2 patients (grade 1 and grade 4); the grade 4 case involved a patient with secondary central nervous system disease who nonetheless achieved a partial response with clearance of malignant cells from cerebrospinal fluid, and whose neurologic symptoms resolved with anakinra. Two deaths occurred: one sudden in-hospital death of uncertain cause the day after the first glofitamab dose, and one from disease progression. Overall, best response across evaluable patients was CR in 4/9 and PR in 3/9, with 6-month progression-free survival and overall survival both 78.8%.

The authors note that their cohort was more heavily pretreated than the pivotal phase 1/2 glofitamab trial (median 4.5 vs. 2 prior lines), likely explaining a lower CR rate (78% overall response versus 85% in the trial).³ They emphasize that the bridging-therapy findings are consistent with growing evidence that prior bispecific antibody exposure does not impair, and may even enhance, subsequent CAR T-cell efficacy, supporting the feasibility of sequential immunotherapy in relapsed/refractory MCL.

However, the authors caution that more studies are needed.

“These retrospective real-world results suggest encouraging clinical activity of glofitamab in heavily pretreated patients with R/R MCL with a manageable safety profile and predominantly low-grade CRS,” the authors wrote. “Responses were also observed in patients treated after CAR T-cell therapy failure and in patients receiving glofitamab as bridging therapy to CAR T-cell therapy.

“However, given the retrospective nature, small sample size and short follow-up, these data should be interpreted with caution. Larger prospective trials are needed to further define the role of glofitamab monotherapy in R/R MCL.”

References

1. Rotter N, Raderer M, List A, et al. Glofitamab in heavily pretreated mantle cell lyphoma patients: a multicenter real-world case series. eJHaem. 2026;7(4):e70343. doi: 10.1002/jha2.70343.
2. European Commission approves Roche’s fixed-duration Columvi (glofitamab) for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Roche. July 11, 2023. Accessed July 20, 2026. https://www.roche.com/media/releases/med-cor-2023-07-11
3. Phillips TJ, Carlo-Stella C, Morschhauser F, et al. Glofitamab monotherapy in patients with heavily pretreated relapsed/refractory (R/R) mantle cell lymphoma (MCL): Uupdated analysis from a phase 1/2 study,” J Clin Oncol. 2024; 42(suppl 16):abstr 7008.