Abstract
Background: Epcoritamab (EPCO), a CD3xCD20 bispecific antibody, has emerged as a promising therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), including those who have progressed after CAR T-cell therapy. In the pivotal EPCORE NHL-1 trial, epcoritamab demonstrated an overall response rate of 63%, with deep and durable responses in high-risk and heavily pretreated populations. However, real-world data on survival outcomes, toxicity, and treatment-related complications remain limited. This study aimed to evaluate real-world outcomes of epcoritamab using the TriNetX global health research network.
Methods: We conducted a retrospective study of patients with R/R DLBCL treated with epcoritamab between database inception and June 2025 using the TriNetX global health research network. The analysis included data from 172 million patients across 151 healthcare organizations worldwide, predominantly academic centers in the U.S. Eligible patients had a confirmed diagnosis of R/R DLBCL, received ≥2 prior lines of systemic therapy including CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel), were treated with epcoritamab, had an ECOG performance status of 0–2, and had ≥30 days of follow-up. Patients with a history of stem cell transplants were excluded. Outcomes included 6-month overall survival (OS), hematologic toxicities, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Adverse events were graded per CTCAE v5.0. Kaplan-Meier analysis was used to estimate OS; other outcomes were reported as proportions.
Results: A total of 234 patients met inclusion criteria. The mean age was 69 ± 12.6 years; 58.97% were male and 67.94% were White. Median follow-up was 163.5 days. At 6 months, the OS probability was 65.5% (95% CI: 59.4%–71.6%), with a mortality rate of 29.5%, consistent with outcomes reported in the EPCORE NHL-1 trial. Grade ≥3 cytopenias were frequent: neutropenia (40.2%), anemia (40.2%), and thrombocytopenia (32.1%). Grade 3–4 CRS and ICANS occurred in ~4.1% of patients, and 25% received tocilizumab. Common non-hematologic complications included cardiovascular events (atrial fibrillation 17%, heart failure 13%), infectious complications (pneumonia/influenza 23%, COVID-19 9%, CMV reactivation 4%), and constitutional symptoms (fever 26%, malaise/fatigue 18%).
Conclusion: In this real-world cohort, epcoritamab demonstrated favorable short-term survival in patients with R/R DLBCL following CAR T-cell therapy, mirroring results from the EPCORE NHL-1 trial. By limiting the cohort to patients with ECOG 0–2 and excluding prior transplant recipients, the study population closely resembled clinical trial eligibility. These findings support the broader applicability of epcoritamab in routine practice and highlight the importance of early recognition and management of toxicities. Prospective validation is warranted.
