SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Hematologic Malignancies
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1641769
CD20×CD3 bispecific antibody achieved significant efficacy in patients with large B-cell lymphoma relapsing after or refractory to CAR-T therapy: a systematic review and meta-analysis
Provisionally accepted- 1Capital Medical University Affiliated Beijing Friendship Hospital, Beijing, China
- 2Shenyang Pharmaceutical University, Shenyang, China
- 3National University of Defense Technology, Changsha, China
- 4Sichuan University West China School of Medicine, Chengdu, China
- 5961 Hospital of Join Logistic Support Force, Qiqihar, China
- 6General Hospital of Northern Theatre Command, Shenyang, China
- 7Northern Theater Command General Hospital, Shenyang, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: Chimeric antigen receptor T-cell immunotherapy (CAR-T) is a preferred treatment for relapsed or refractory (R/R) large B-cell lymphoma (LBCL).Several trials have evaluated CD20×CD3 bispecific antibodies (BsAbs) as subsequent therapy in R/R LBCL. This study aimed to investigate the efficacy of CD20×CD3 BsAbs (mosunetuzumab, glofitamab, odronextamab, and epcoritamab) in patients with LBCL who experienced relapse or refractory disease following CAR-T therapy.Methods: Nine trials involving 350 participants were included, assessing the overall response rate (ORR), complete response (CR), duration of response (DOR), duration of complete response (DoCR), progression-free survival (PFS), and overall survival (OS).Results: The specific response rates for different bispecific antibody (BsAb) monotherapies were as follows: ORR 40% and CR 23%; Glofitamab: ORR 50-76.1% and CR 37-45.7%; Epcoritamab: ORR 54.1% and CR 36%; Odronextamab: ORR 48.3% and CR 31.7%. Upon pooled analysis, the overall ORR was 54.5% (95% CI: 43.1-65.7%) with significant heterogeneity (P=0.013, I²=68.24%), and the CR was 35.6% (95% CI: 29.1-42.2%) with low heterogeneity (P=0.33, I²=13.5%). The specific response rates for different BsAb combinations were as follows: Mosunetuzumab + Pola: ORR 57% and CR 40%; Glofitamab + Pola: ORR 77.8% and CR 44.4%; Epcoritamab + Gemox: ORR 76% and CR 45%; Glofitamab + Gemox: CR 53.8%. Upon pooled analysis, the overall ORR was 70.0% (95% CI: 56.4-82.2%) with no heterogeneity, and the CR was 44.2% (95% CI: 34.5-54.1%) with no heterogeneity. The median duration of follow-up ranged from 13 to 42 months. Data from five trials were available for DOR analysis: 9.7 months, 14.8 months, 19.7 months, not reached, and 2-year rate of 25%, respectively; three trials were available for DoCR analysis: one trial reported 22 months, and the others were not reached; six trials were available for mPFS analysis: 3.8 months, 4.8 months, 6.1 months, 9.6 months, 13.7 months, and 31.1 months, respectively; three trials were available for mOS analysis: 10.2 months, 14.7 months, and not reached, respectively.Conclusion: CD20×CD3 BsAbs exhibit efficacy in R/R LBCL patients following CAR-T therapy. To validate these findings and determine the optimal sequencing of BsAbs and CAR-T therapy for R/R LBCL patients, prolonged follow-up periods and further prospective clinical trials are warranted.
Keywords: bispecific antibody, Meta-analysis, CAR-T cell therapy, Relapsed and refractory, Large B-cell lymphoma
Received: 05 Jun 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Shen, Zhang, Zhu, Ma, Li, Zhang, Zhou, Tian and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jinghua Liu, Northern Theater Command General Hospital, Shenyang, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.