LCL-161 combined with chemotherapy can extend survival compared with chemotherapy alone in an animal model of rituximab-resistant lymphoma. Animals were inoculated with 1 × 106 Raji cells or with 10 × 106 Raji 4RH cells via tail vein injection (IV). Treatment was administered 7 days after xenograft implantation. Treatment groups were LCL-161 alone (60 mg/kg orally), RGV, or a combination of RGV+LCL-161. (A) SCID mice inoculated with the Raji cell line responded very well to RGV, with 100% survival. LCL-161 provided no additional benefit when added to RGV. (B) SCID animals inoculated with the Raji 4RH cell line had much poorer responses to RGV alone, although the addition of LCL-161 to RGV increased survival durations to a statistically significant degree. (C) Median survival duration by treatment. ±P > .05 vs control, ‡P = .006, RGV alone vs RGV+LCL-161, log-rank test. + = censored value. 95% CI, 95% confidence interval.