Epcoritamab achieves durable remission after CD20 antigen escape in primary cardiac diffuse large B-cell lymphoma

CD20 antigen loss after anti-CD20-based therapy is a mechanism of immune escape in diffuse large B-cell lymphoma (DLBCL). Emerging real-world data have shown that patients with undetectable CD20 expression who are treated with CD20-targeting bispecific antibodies may have inferior outcomes. Herein, we report a 77-year-old female patient with primary cardiac DLBCL who exhibited cardiac tamponade. The patient's CD20 expression was weak based on immunohistochemistry but was clearly positive on flow cytometry (79.2%) upon diagnosis. She received dose-reduced rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin, followed by polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone. However, she developed primary refractory disease with recurrent cardiac tamponade and embolic cerebral infarction, with near-complete loss of CD20 expression according to both immunohistochemistry and flow cytometry (0.1%) on rebiopsy. The patient was not eligible for autologous stem cell transplantation and chimeric antigen receptor T-cell therapy as she personally refused blood transfusions. After one cycle of salvage gemcitabine, carboplatin, and dexamethasone, epcoritamab therapy was initiated. Catecholamine support was discontinued on day 16 of cycle 1, and hemodynamic stability was achieved on day 22. Pericardial effusion completely resolved by the end of cycle 1. Epcoritamab has been continued for > 8 months without significant adverse events, and the patient remains in computed tomography scan confirmed complete remission. Based on this case, epcoritamab may retain clinically significant activity despite undetectable CD20 expression, and CD20 negativity alone should not automatically preclude its use in refractory DLBCL.