Remission of Chimeric Antigen Receptor T-Cell-Refractory Diffuse Large B-Cell Lymphoma Resolved by Surgery and CD20 Bispecific Therapy

Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. Some patients who progress after frontline chemoimmunotherapy can be cured with chimeric antigen receptor (CAR) T-cell therapy, though its success remains limited. While promising, the majority of patients relapse after CAR T-cell therapy, and there is no accepted standard of care. In the following case report, we present a patient with primary refractory DLBCL with an isolated bulky recurrence in his proximal thigh that did not respond to local radiation therapy, progressed after cluster of differentiation (CD)19 and CD22 directed autologous CAR T-cell therapy, and initially failed to respond to CD20 bispecific T-cell engager epcoritamab. He underwent complete surgical excision of the localized lesion followed by resumption of epcoritamab as maintenance therapy, leading to a durable remission. While surgery is not typically considered therapeutic for DLBCL, this case highlights the potential value of surgical debulking in DLBCL with an isolated recalcitrant lesion. We also discuss the potential influence of the tumor microenvironment and the use of surgery in complex cases like this.