Ibrutinib and lenalidomide may augment the activity of DA-EPOCH-R via inhibition of BCR signaling and NF-κB activation, as both are drivers in non-GCB and ABC DLBCL; thus, the combination of DA-EPOCH-R, ibrutinib, and lenalidomide was evaluated in R/R DLBCL. The gene discussed is BCR; the disease is diffuse large B-cell lymphoma.