IL-6 and IL-10 are triggered by sustained ERK1/2 activation in ibrutinib-treated BTK^Cys481Serexpressing cells and can be abrogated by ERK1/2 inhibitors. BTK^WT and BTK^Cys481Ser expressing BCWM.1 WM or TMD8 ABC DLBCL cells were treated with ibrutinib, ulixertinib, or GDC-0994 alone or in combination and assessed for IL-6 and IL-10 mRNA expression by TaqMan Gene Expression Assays. BTK^Cys481Ser expressing BCWM.1 WM and TMD8 ABC DLBCL cells showed sustained IL-6 (A,C) and IL-10 (B,D) transcription following ibrutinib treatment that was abrogated by the ERK1/2 inhibitors ulixertinib and GDC-0994. ***P < .001; **P < .005; NS, not significant (P ≥ .05).