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.
Bispecifics After CAR T: Real-World Signals in MCL
- In a multicenter real-world analysis, CD20-targeted bispecific antibodies showcased meaningful clinical activity following CD19-targeted CAR T-cell therapy in patients with heavily pretreated mantle cell lymphoma.
- Responses were observed across regimens, with particularly high response rates seen with mosunetuzumab plus polatuzumab vedotin, although follow-up remains short.
- Outcomes were notably poorer in patients who experienced early relapse after CAR T-cell therapy, underscoring the need for more effective strategies in this high-risk subgroup.
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.
