The combination of epcoritamab with venetoclax induced a higher degree of CLL cytotoxicity in vitro than either agent alone. PBMCs from patients who were TN (n = 15), patients treated with BTKi (BTKi, n = 11; IBR, 4; and ACA, 7), and patients who were RES (n = 9) were cultured with either B12/dimethyl sulfoxide control (CTRL), epcoritamab (EPCO), 5nM venetoclax (VEN), or the combination of epcoritamab with venetoclax (EPCO + VEN). (A) CLL cell viability after 7 days of culture. (B) Spearman correlation of baseline E:T ratios and percentage of CLL cell–specific lysis in samples from all 3 groups cultured with EPCO + VEN for 7 days. Asterisks indicate statistical significance using Wilcoxon matched-pair signed rank test for the comparison of different treatments applied to individual patient samples. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.