Real-world outcomes of epcoritamab vs glofitamab in relapsed/refractory diffuse large B-cell lymphoma: A TriNetX retrospective study.

7037 Background: Glofitamab and epcoritamab are CD20-directed bispecific antibodies that engage CD3-positive T cells and are approved for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). While trials reported high response rates, real-world comparative data on survival, safety, and treatment complications are limited. We conducted a propensity score-matched analysis to compare the effectiveness and safety of glofitamab and epcoritamab in R/R DLBCL. Methods: We conducted a retrospective cohort study of adult relapsed/refractory diffuse large B-cell lymphoma patients treated with glofitamab or epcoritamab through January 2026 using the TriNetX network. Eligible patients had confirmed R/R DLBCL, ≥2 prior systemic therapies and ≥30 days follow-up. Data from 134 million patients across 70 US healthcare organizations were analyzed. Propensity-score matching was done for age, sex, race, comorbidities, prior CAR T, and prior therapies. Outcomes included overall survival, all-cause mortality, hematologic adverse events, CRS, ICANS, infections, and ICU admissions. Results: A total of 369 epcoritamab and 337 glofitamab patients met the inclusion criteria. After 1:1 propensity-score matching, 205 patients were included in each cohort. Median age was 68 years for glofitamab and 67.8 years for epcoritamab, with 62.9% vs 64.9% male. Median follow-up was 6.8 months vs 5.8 months. At 6 months, mortality was 29.3% versus 39.0% (RR 0.75, 95% CI 0.57-0.99; p=0.037), with estimated overall survival 68.1% versus 55.8% (HR 0.68, 95% CI 0.49-0.95; p=0.023). This benefit persisted at 12 and 24 months (estimated overall survival 54.0% vs 43.8% and 37.5% vs 33.3%, HR 0.73-0.75), though fixed-time risk differences were not significant. Any-grade CRS occurred in 22.4% vs 30.2% (RR 0.74, 95% CI 0.53-1.03; p=0.073), with grade ≥3 CRS not significantly different between cohorts. ICANS occurred in 7.3% vs 11.7% (RR 0.63, 95% CI 0.34-1.16; p=0.130), and tocilizumab use was comparable (20.0% vs 22.0%). Hematologic adverse events, including neutropenia (21.5% vs 26.8%), thrombocytopenia (34.1% vs 35.1%), anemia (35.1% vs 40.0%), and ICU admissions (19.0% vs 25.4%), were comparable and not significantly different. Infections were significantly lower with glofitamab (38.0% vs 48.8%, RR 0.78, 95% CI 0.62-0.98; p=0.028), supporting a favorable safety profile. Conclusions: In this real-world analysis, glofitamab and epcoritamab had similar safety profiles, with glofitamab showing lower early mortality and higher overall survival. Hematologic adverse events, CRS, ICANS, and ICU admissions were comparable, while infections were significantly lower with glofitamab. The selection of CD20×CD3 bispecific antibodies should consider infection risk and early survival outcomes until longer follow-up clarifies durability and late toxicities.