Patient Outcomes After Epcoritamab or Glofitamab Failure in Relapsed or Refractory LBCL
Key Clinical Summary
- Over half (53.8%) of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab or glofitamab experienced disease progression, often within weeks of initiation.
- Median progression-free survival after subsequent therapy was 1.9 months, with median overall survival (OS) of 3.9 months and 1-year OS of 12%.
- Nearly 42% of patients received no further treatment after progression, underscoring a major unmet need.
Epcoritamab and glofitamab are approved bispecific antibodies (BsAbs) for R/R LBCL, yet outcomes following disease progression remain poorly characterized. In a multicenter US retrospective study (2023-2025), investigators evaluated treatment patterns and survival outcomes after progression on BsAbs, revealing limited efficacy of subsequent therapies and poor survival in this high-risk population.
Study Findings
This retrospective analysis included 312 patients with R/R LBCL treated with commercially available epcoritamab or glofitamab across 21 US centers. Of these, 168 patients (53.8%) experienced progression of disease (POD), with identical progression rates observed between epcoritamab (104/193) and glofitamab (64/119).
Patients with POD had a median age of 67 years, and 68.4% were male. Diffuse large B-cell lymphoma, not otherwise specified, accounted for 71.8% of cases. Notably, 39.9% had primary refractory disease, and 60.7% had previously received chimeric antigen receptor (CAR) T-cell therapy—of whom one-third were refractory and 30.4% relapsed within 6 months.
Progression occurred rapidly, with a median time to progression of 48 days from BsAb initiation. Following progression, 70 patients (41.7%) received no further therapy. Among the 98 patients who did, most (85) received systemic therapy, while 13 received radiation-based approaches.
Response rates to subsequent therapies were modest. Loncastuximab tesirine yielded an overall response rate (ORR) of 16.7% (all partial responses), while CAR T-cell therapy achieved a 50% ORR, including 36.4% complete responses. Tafasitamab plus lenalidomide showed no responses, and chemotherapy produced an ORR of 27.6% with 24.1% complete responses.
Despite these interventions, outcomes remained poor. Median progression-free survival after next-line therapy was 1.9 months, and median overall survival was 3.9 months. The estimated 1-year overall survival rate was only 12%.
Clinical Implications
These findings highlight a critical gap in effective treatment options for patients with R/R LBCL who progress after bispecific antibody therapy. Although BsAbs offer meaningful initial responses, durability remains limited, with rapid progression observed in many patients.
The low response rates and short survival following subsequent therapies emphasize the aggressive nature of disease in this setting. Notably, a substantial proportion of patients did not receive additional treatment, which may reflect poor performance status, limited options, or rapid clinical decline.
CAR T-cell therapy demonstrated relatively higher response rates compared with other approaches, suggesting a potential role even after BsAb exposure. However, outcomes remain suboptimal overall, reinforcing the need for better sequencing strategies and novel therapeutic combinations.
These results support prioritizing clinical trial enrollment for patients progressing after BsAbs. Investigational therapies, including next-generation immunotherapies and combination regimens, may be necessary to improve outcomes in this population.
Investigators concluded that “progression events occurred early after initiation of single-agent BsAbs, and almost half of patients who progressed did not receive subsequent therapy.” They emphasized that “response rates and survival outcomes were poor” with standard approaches, underscoring the urgency of developing new treatment strategies for this high-risk group.
Conclusion
Patients with R/R LBCL who progress after bispecific antibody therapy face poor outcomes and limited treatment options. Early progression and low survival rates highlight the need for clinical trials and novel therapeutic strategies to improve care in this setting.
Reference
Brooks T, Mian A, Nedved A, et al. Outcomes following disease progression after epcoritamab or glofitamab in the real-world outcomes of bispecific T-cell engagers (REALBiTE) multi-center, retrospective cohort study. Presented at: ASH 2025; December 6-9; Orlando, FL.
