Heavily Pretreated Refractory Diffuse Large B-Cell Lymphoma Successfully Treated with Epcoritamab: Case Report

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) poses considerable treatment challenges, with disheartening odds of long-term survival. Numerous strategies exist, including non-cross-resistant combination chemoimmunotherapy regimens, autologous stem cell transplantation, and chimeric antigen receptor (CAR) T-cell therapy, but some patients are not appropriate candidates or cannot sustain response to treatment. Epcoritamab, a bispecific CD20-directed CD3 T-cell engager, has been given accelerated approval by the US Food and Drug Administration for relapsed or refractory DLBCL.

We present the case of a 61-year-old male diagnosed with stage 4 "double-hit" DLBCL with MYC and BCL6 rearrangement, who initially received one cycle of rituximab HyperCVAD (initiated July 23, 2021). He then received dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) followed by high-dose methotrexate and initially responded but relapsed several months later. As the patient was not a candidate for transplant, subsequent treatment rounds included rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) and CD19 CAR T-cell therapy; tafasitamab-cxix and lenalidomide; and polatuzumab vedotin plus bendamustine and rituximab (pola-BR). Despite intermittent treatment response, his disease continued to progress. He began treatment with epcoritamab through the early access program but showed early signs of continued progression; his status deteriorated until further treatment had to be withheld. Within approximately 1 month, he could resume treatment, achieving a Deauville score of 1 approximately 3 months after beginning epcoritamab, and continues follow-up nearly 2 years later.

T-cell engager therapies, such as epcoritamab, can play a role in managing patients with refractory DLBCL, including those refractory to CAR T-cell therapy.