IBR and VEN are variably cytotoxic in CLL and MCL patient PBMCs. (A) Representative images showing cleaved PARP in CD5⁺/CD19⁺ cells in CLL (patient [Pt] 12) and MCL (Pt 22) patient PBMCs following ex vivo treatment with IBR (0.1 μM), VEN (25 nM), or IBR+VEN. The concentrations of IBR and VEN that showed 20% to 30% cytotoxicity as single agents (measured by alamarBlue) in a CLL patient PBMC were selected for ex vivo treatment of patient samples (data not shown). (B-D) PBMCs from CLL (N = 24) and MCL (N = 8) patients were treated with IBR, VEN, or IBR+VEN. The cleaved PARP in CD5⁺/CD19⁺ cells in CLL samples showing synergy (B) or no synergy (C) with IBR+VEN and in MCL samples (D) is shown. Comparable results were also obtained by analyzing the dead cell staining of CD5⁺/CD19⁺ cells in CLL and MCL patient PBMCs: samples that exhibited synergistically high cleaved PARP also showed synergistic increases in dead cell staining following ex vivo treatment with IBR and VEN (supplemental Figure 2A-C). The time to achieve maximal synergistic cytotoxicity (∼6-18 hours) was chosen as the time point used for subsequent data analysis. Synergy was calculated using the Bliss model of independence, which generates interaction scores even where 1 drug has no effect. Data are expressed as means ± SD. Statistical significance was determined by ANOVA. *P < .05, **P < .01, ****P < .0001. NS, not significant; SSC, side scatter.