IMMU-03. Sustained anti-PD1 response in refractory EBV-positive DLBCL with CNS involvement in an immunocompetent patient

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive form of non-Hodgkin lymphoma, accounting for 30–40% of cases. Epstein-Barr virus (EBV)-positive DLBCL is a rare, more aggressive subtype, comprising 7–8% of cases and marked by EBV within tumor cells. It is more common in elderly and immunocompromised patients. While typical DLBCL presents with lymphadenopathy and constitutional symptoms, EBV-positive DLBCL often presents at an advanced stage, with more frequent extranodal disease. Furthermore, EBV-positive DLBCL with central nervous system (CNS) involvement typically presents with multifocal lesions, responds poorly to standard treatment, and is associated with a poorer overall prognosis. Here, we describe the case of a 58-year-old immunocompetent male with EBV-positive, non-germinal center B-cell (non-GCB) DLBCL with synchronous pulmonary and CNS involvement. His disease was refractory to MR-CHOP (high-dose methotrexate, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), as well as to R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) combined with intrathecal methotrexate (IT-MTX). Given that his tissue demonstrated >70% of neoplastic B cells positive for PD-L1 staining, the patient was started on anti-PD-1 (anti-programmed cell death protein 1) therapy with nivolumab (240 mg every 14 days for three doses) as a bridge to CAR-T cell therapy. The patient developed severe immune-checkpoint inhibitor encephalitis with status epilepticus and hypothalamic dysfunction which was treated with intravenous methylprednisolone and intravenous immunoglobulins. Notably, his disease experienced a rapid and sustained response to the PD-1 blockade and he has remained disease-free four years later. He remains clinically stable, with occasional hypothermia from his hypothalamic injury. This case is notable for (1) a rare presentation of EBV-positive DLBCL with CNS involvement in an immunocompetent patient (2) a successful clinical response to anti-PD-1 therapy in refractory disease (3) further support for high PD-L1 expression and EBV positivity as predictors of response to anti-PD-1 therapy.