AZD8835 and ibrutinib act synergistically in ABC DLBCLs. (A) AZD8835 and ibrutinib in vitro treatment of OCI-Ly10, TMD8, HBL-1, and OCI-Ly3 cells. Combinatorial treatment induces synergistic cytotoxicity in OCI-Ly10, TMD8, and HBL-1 cells. In contrast, OCI-Ly3 cells are affected by neither single nor combined inhibitor treatment. (B) Tumor growth curves of OCI-Ly10 and TMD8 xenograft mouse models and of the non-GCB DLBCL PDX model KTC following treatment with either vehicle control, AZD8835 alone, ibrutinib alone, or with both AZD8835 and ibrutinib. Combined inhibitor treatment with AZD8835 and ibrutinib reduces tumor growth significantly more compared with AZD8835 alone (P = .002 for AZD8835 [n = 9] vs AZD8835/ibrutinib [n = 10] on day 11 in OCI-Ly10; P = .001 for AZD8835 [n = 10] vs AZD8835/ibrutinib [n = 10] on day 22 in TMD8; P = 1.22 × 10⁻⁵ for AZD8835 [n = 8] vs AZD8835/ibrutinib [n = 8] on day 18 in KTC; 1-tailed 2-sample Student t tests). Treatment was initiated after animals developed macroscopic signs of tumors (day 24 after engraftment in OCI-Ly10; day 6 after engraftment in TMD8; day 15 after engraftment in KTC). Error bars indicate the standard error of the mean. The arrow indicates end of treatment with AZD8835 and AZD8835/ibrutinib in the KTC PDX model. **P < .01; ***P < .001.