The combination of drugs frequently used to treat B-cell malignancies with iBETs enhances the killing of primary B-PLL cells with t(MYC). (A) B-PLL cells from 3 patients with t(MYC) were treated with the indicated concentrations of ibrutinib, idelalisib, venetoclax, or fludarabine in the presence or absence of OTX015 (500 nM). Viability was assessed with an ATP-based CellTiter-Glo 2.0 kit. (B) B-PLL cell viability was measured and analyzed as in panel A in a patient with del17p but no MYC aberration. (C) Cell death was quantified in primary B-PLL cells from patient BPLL_8 [with t(MYC)] with or without pretreatment with OTX015 (500 nM) and exposure for 48 hours to ibrutinib (7.5 µM), idelalisib (50 µM), or venetoclax (10 nM). The percentages refer to Annexin-V–positive or Annexin-V–/propidium iodine–positive cells. (D) Primary B-PLL cells from BPLL_34 (with del17p but no MYC aberration) were treated with drugs and analyzed as in panel C. Bars represent the mean ± SEM.