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. This evidence concerns the gene NFKB1 and aneurysmal bone cyst.