Ibrutinib has a strong on-target effect in tissue-resident CLL cells. (A) BTK occupancy in lymph node (LN) biopsies on day 2 compared with pretreatment as determined by probe assay. Each dot represents a different patient (n = 6). (B-C) Percent reduction in BCR and NF-κB signature scores in either (B) LN biopsies (n = 24) or (C) CLL cells purified from bone marrow (BM) aspirates (n = 8). The line represents the median. (D) Correlation of reduction in BCR and NF-κB signature scores in LN biopsies (n = 24). (E-F) Mononuclear cells from LN biopsies (n = 8) or BM aspirates (n = 10) were fixed, permeabilized, and stained with the indicated antibody. Results shown are for the CLL population (CD5⁺/CD19⁺). The mean (± SEM) percent of (E) pPLCγ2 and (F) pERK expressing CLL cells pretreatment (Pre) and on ibrutinib is shown.