Successful Use of Epcoritamab in Refractory High-Grade Diffuse Large B-Cell Lymphoma with Central Nervous System Involvement: A Case Report

We describe the case of a 71-year-old man with primary bone marrow high-grade diffuse large B-cell lymphoma (DLBCL) that was refractory to dose-adjusted EPOCH-R. Despite high-dose methotrexate and intrathecal chemotherapy, the disease progressed rapidly with central nervous system (CNS) involvement. Given the limited efficacy of standard salvage regimens and the urgency of disease control, epcoritamab, a CD20×CD3 bispecific antibody, was introduced with bridging therapy. Bispecific antibodies are generally considered ineffective in CNS disease due to poor blood–brain barrier penetration, and such patients are usually excluded from clinical trials. In this patient, however, epcoritamab achieved a rapid systemic response and partial neurological improvement. His history included splenectomy, which may have contributed to disease localization in the bone marrow and its aggressive clinical course. This case highlights the potential of bispecific antibody therapy in refractory high-grade DLBCL with CNS involvement, an area of significant unmet need.