Epcoritamab (CD3×CD20 bispecific) + R-CHOP Drives 85% CR and 80% 2-year PFS in High-Risk Newly Diagnosed LBCL

Epcoritamab is a subcutaneous CD3×CD20 bispecific T-cell–engaging antibody added to standard R-CHOP, aiming to deepen frontline remissions in CD20+ large B-cell lymphoma (LBCL). In Arm 1 of the Phase 1b/2 EPCORE NHL-2 trial (NCT04663347), newly diagnosed LBCL patients with high-risk IPI 3-5 received 6 cycles of R-CHOP plus epcoritamab (total planned treatment duration 1 year); 47 patients were treated (median age 64; 89% stage IV; 53% bulky ≥7 cm), with ORR 98% and CR 85%. With 44.2 months’ median follow-up, median PFS/OS were not reached and 2-year PFS/OS were 80%/87%; MRD negativity was 100% among MRD-evaluable patients, while safety showed high cytopenias (neutropenia 74%, anemia 72%) and CRS in 60% (predominantly grade 1-2, all resolved) — compared with R-CHOP alone in higher-risk DLBCL where long-term PFS is typically ~50%-60% in poor-risk groups and polatuzumab-R-CHP (a current frontline alternative for intermediate/high-risk disease) delivers a more modest absolute PFS gain vs R-CHOP (exploratory IPI 3-5 subgroup HR ~0.71 in POLARIX).