Abstract

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the treatment landscape for relapsed or refractory non-Hodgkin lymphoma, achieving a 5-year overall survival rate of 40-50%. However, relapse remains a major challenge, especially due to CD19-negative clones. Epcoritamab, a bispecific antibody targeting CD20 and CD3, offers a potential solution for post-CAR-T relapse; however, clinical data in this setting remain limited, particularly in Japan.

The case: A 68-year-old woman with CD5-positive diffuse large B-cell lymphoma (DLBCL) relapsed multiple times following various treatments, including CAR-T therapy. Genetic profiling revealed a MYD88/CD79B-mutated (MCD) subtype with CD19-negative clones resistant to CAR-T cells. Given her high tumor burden, she received debulking therapy followed by epcoritamab treatment. Despite concerns about tumor lysis syndrome, cytokine release syndrome, and neurotoxicity, no significant adverse events occurred. The patient achieved a complete remission, demonstrating the efficacy and safety of this approach.

Conclusion: This case highlights the potential of epcoritamab combined with debulking therapy for treating CAR-T-refractory CD19-negative DLBCL. This is the first validated case in Japan showing that epcoritamab is a viable and safe treatment option for post-CAR-T relapse, addressing a critical unmet need in the current therapeutic landscape.