In this report, we present a case of a patient with DLBCL who was refractory to multiple lines of systemic therapy including radiation therapy and CD19 and CD22 CAR T-cell therapies with a persistent and enlarging soft tissue mass of his thigh who achieved durable remission through a multifactorial strategy including surgical resection of the thigh mass and maintenance epcoritamab. The gene discussed is CD22; the disease is diffuse large B-cell lymphoma.