Real-World Analysis Sheds Light on Bispecific Antibody Activity After CAR T in Mantle Cell Lymphoma

Data from a real-world multicenter analysis shared during the 2026 Transplantation and Cellular Therapy Meetings suggested that CD20-targeted bispecific antibodies (BsAbs) had activity after CD19-targeted CAR T-cell therapy in patients with mantle cell lymphoma, although longer follow-up is needed to understand the durability of response.¹

In the entire cohort (n = 20), the objective response rate achieved with BsAbs was 70%, which included a complete response (CR) rate of 45%. At a median follow-up of 8.9 months, the median duration of response (DOR) had not yet been reached (NR), the median progression-free survival (PFS) was 8.9 months, and the median overall survival was also NR.

When broken down further, those who received mosunetuzumab-axgb (Lunsumio)/polatuzumab vedotin-piiq (Polivy; n = 9) achieved an ORR of 76% with a CR rate of 56% with BsAbs. At a median follow-up of 8.9 months, the median DOR was 7.5 months, the median PFS was 8.9 months, and the median OS was NR. Those who received glofitamab-gxbm (Columvi; n = 11) experienced an ORR of 64%, which included a CR rate of 36% with BsAbs. At a median follow-up of 8.9 months, the median DOR, PFS, and OS were all NR. Lastly, in those who received brexucabtagene autoleucel (Tecartus; brexu-cel; n = 10), the ORR was 60%, and the CR rate was 50%; at a median follow-up of 12.7 months, the median DOR was NR, the median PFS was 4.3 months, and the median OS was NR.

Additional data indicated that outcomes were inferior among patients who experienced early relapse after CAR T exposure (n = 10). In these patients, the median DOR was 7.5 months, the median PFS was 3.3 months, and the median OS was 7.6 months. In comparison, those with late relapse to CAR T (n = 10) experienced a median DOR (P = .57), PFS (P = .065), and OS (P = .13) that was NR.

“These data support further development of BsAb in the post–CAR T setting, especially combination regimens such as mosunetuzumab/polatuzumab vedotin, but highlight the pressing need for improved therapeutics for patients with early relapse,” Ajay Major, MD, MBA, of the University of Colorado Anschutz, and coauthors, wrote in a poster of the data.

What inspired the multicenter analysis of BsAbs in mantle cell lymphoma? What was the design of the research?

For patients with mantle cell lymphoma, emerging therapeutic options include BsAbs like mosunetuzumab² and glofitamab.³ Although these agents are efficacious, there are limited data to shed light on the real-world safety and activity of these agents after prior exposure to CD19-targeted CAR T-cell therapy. To this end, investigators set out to conduct the retrospective multicenter study, which specifically assessed the use of BsAbs in those who were diagnosed with mantle cell lymphoma and who were receiving treatment at 10 medical centers throughout the United States. Of the 31 total patients with this disease who received treatment at the centers that comprised the Collaborative US Bispecific Consortium, 20 were administered BsAbs post CAR T-cel therapy and were included in the analysis shared at the meeting.

Investigators descriptively analyzed demographics, disease and treatment characteristics, as well as adverse effects (AEs). They defined early relapse as having experienced disease progression in less than 6 months after receipt of CAR T cells. By leveraging Kaplan-Meier analysis, DOR, PFS, and OS were evaluated. Moreover, survival outcomes were evaluated for the entire cohort and specifically for the subset of patients who had been given brexu-cel.

In the entire cohort of 20 patients, the median age was 64 years (range, 48-85), and most were male (80%). The median ECOG performance status of patients was 1 (range, 0-3). Moreover, patients were fairly heavily pretreated, having received a median of 5 prior lines of therapy (range, 2-9). In terms of the specific CAR T-cell therapies received, half had brexu-cel and half received other CD19-targeted products. In terms of BsAbs received, 45% had received mosunetuzumab plus polatuzumab vedotin, and 55% had received glofitamab.

The median DOR to CAR T-cell therapy was 6 months (range, 3-54) and the median months from CAR T-cell therapy to receipt of BsAbs was 8 months (range, 3-54). Just under half of patients (45%) received a BsAb as their immediate next line of therapy following exposure to CAR T cells, and half of patients experienced early relapse after CAR T-cell therapy.

What was learned about the real-world safety of BsAbs post–CAR T-cell therapy in patients with mantle cell lymphoma?

In the entire cohort, 45% of patients experienced cytokine release syndrome (CRS), and 15% had immune effector cell–associated neurotoxicity syndrome (ICANS). Specifically, of those who experienced CRS, 8 had received glofitamab, and 1 had received the combination of mosunetuzumab and polatuzumab vedotin. All patients who experienced ICANS had received glofitamab.

“Infections were common after BsAb initiation, suggesting cumulative immunosuppression in these heavily pretreated patients and the need for enhanced infectious prophylaxis strategies,” the study authors wrote. Forty-five percent of patients had infections; 3 patients had COVID-19, 2 had cytomegalovirus (CMV) colitis, 2 had Pseudomonas infection, 1 had toxoplasmosis, and 1 had candidemia. Two infections proved fatal (grade 5; toxoplasmosis and CMV colitis).

What’s next for this research with BsAbs in mantle cell lymphoma?

“Analysis of survival outcomes among all patients with MCL who received BsAb in CUBIC, regardless of prior CAR T receipt is planned,” the study authors concluded.

References

1. Major A, Ayers AA, Bair S, et al. Outcomes of CD20 bispecific antibodies after CD19 CAR T-cell therapy in mantle cell lymphoma: A multicenter analysis from the Collaborative US Bispecific Consortium (CUBIC). Presented at: 2026 Transplantation and Cellular Therapy Meetings; February 4-7, 2026; Salt Lake City, UT. Poster ID 517.
2. Budde LE, Matasar M, Sehn LH, et al. Mosunetuzumab monotherapy demonstrates encouraging activity and a manageable safety profile in patients with heavily pre-treated relapsed or refractory mantle cell lymphoma. Blood. 2024;144(suppl 1): 1646. doi:10.1182/blood-2024-197902
3. Phillips TJ, Marek Trněný, Carlo-Stella C, et al. Glofitamab induces high response rates and durable remissions in patients with heavily pretreated relapsed/refractory mantle cell lymphoma, including those with a poor prognosis: subgroup results from a phase I/II study. Blood. 2024;144(suppl 1):1631. doi:10.1182/blood-2024-200018