Epcoritamab induces a high degree of CLL cytotoxicity in vitro that is enhanced by prior treatment with BTKis. CLL cell viability was assessed in PBMCs from patients with CLL after culture with either epcoritamab or the B12 nontargeting control antibody (6.6nM): treatment-naive (TN); n = 13, triangles); ibrutinib-treated (IBR; n = 12, circles); acalabrutinib-treated (ACA; n = 14, diamonds) patients; and patients with progressing disease while receiving a BTKi (RES; n = 7). CLL cell viability (A) after 3 and (B) after 7 days in culture with B12 or epcoritamab. (C) Percentage of specific lysis of CLL cells by epcoritamab was calculated as follows: ([%B12-treated CLL viability – %epcoritamab-treated CLL viability] ÷ [%B12-treated CLL viability] × 100). Asterisks indicate statistical significance using Wilcoxon matched-pair signed rank test for comparison of different treatments applied to individual patient samples and Mann-Whitney test for the comparison of different patient groups. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001.