Regarding immunomodulators and cereblon modulator agents, genome-scale CRISPR–Cas9 screenings, performed in cell lines of DLBCL and primary effusion lymphoma (PEL), have shown that not only is the loss of well-defined members or regulators of the E3 ubiquitin ligase complex (CUL4, DDB1, RBX1, CRBN) which interacts with cereblon, possibly associated with resistance, but also that of other genes involved in canonical and noncanonical NF-κB pathways (CYLD, NFKBIA, TRAF2, or TRAF3) or COP9 signalosome (CSN) subunits [67,90]. The gene discussed is CRBN; the disease is diffuse large B-cell lymphoma.