CD22 and diffuse large B-cell lymphoma: 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.