Prognostic factors and survival outcomes in relapsed/refractory aggressive B-cell lymphomas treated with epcoritamab

Epcoritamab is a US Food and Drug Administration-approved bispecific antibody for relapsed/refractory (R/R) large B-cell lymphomas (BCLs). Real-world outcomes and safety data remain limited. We analyzed 157 adult patients with R/R aggressive BCLs who received epcoritamab outside of a clinical trial between 2023 and 2025 at 9 centers in the Collaborative US Bispecific Consortium. The best overall response rate (ORR) was 49.6%, and the best complete response rate (CRR) was 31.9%. With a median follow-up of 15.8 months, the 1-year progression-free survival (PFS) and overall survival (OS) rates among all patients were 29% (95% confidence interval [CI], 22-37) and 38% (95% CI, 31-47), respectively. Inferior ORRs and CRRs were observed in patients with high International Prognostic Index, elevated lactate dehydrogenase (LDH), ≥2 extranodal sites, and disease refractory to the previous line of therapy (LOT). In multivariable analysis, Eastern Cooperative Oncology Group performance status score of ≥2, elevated LDH, refractory disease to previous LOT, and clinical trial ineligibility were associated with inferior PFS and OS. Among all patients, 33% had any-grade cytokine release syndrome (CRS; grade ≥3, 4.6%), whereas immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 12% (grade ≥3, 0.6%) of patients. Intensive care unit (ICU) admission occurred in 17% of patients. Compared with pivotal trials and other real-world studies, we observed inferior response rates and survival outcomes as well as higher rates of grade ≥3 CRS, any-grade ICANS, and ICU admission.