LCL-161 has a synergistic antitumor effect with chemotherapy agents in RRCLs and sensitive parent cell lines. (A) The RRCL Raji 4RH and its sensitive parent cell line Raji were incubated with gemcitabine in combination with LCL-161 for 48 hours at the doses indicated. Viability measurements were performed with the CellTiter-Glo assay. LCL-161 synergistically enhanced the antitumor activity of 50-μM gemcitabine in the Raji 4RH cell line, but it was less effective in Raji cells. (B) A CI synergism calculation, performed with CalcuSyn software, indicated limited synergy in the Raji cell line; however, robust synergy (CI < 0.1) was observed between gemcitabine and LCL-161 in the RRCL Raji 4RH. (C) The antitumor effect of LCL-161 combined with carfilzomib at 24 hours was fairly consistent between Raji and Raji 4RH cells. (D) Synergy was observed in the Raji cell line at most concentrations of LCL-161 and carfilzomib. Stronger synergy values between LCL-161 and carfilzomib were observed in the Raji 4RH cell line compared with the Raji cell line. These results indicate that LCL-161 is more active in the Raji 4RH RRCL model.