Ibrutinib prolongs survival in xenograft models of human ALL. (A) Engraftment and expansion of ICN12-induced leukemia in mice treated with ibrutinib or vehicle control as visualized by luciferase bioimaging. (B) Kaplan-Meier curve demonstrates significantly longer overall survival of ibrutinib-treated mice in a ICN12 human ALL model when compared with control mice (7 per group). (C) Kaplan-Meier curve demonstrates significantly longer overall survival of ibrutinib-treated mice in a RCH-ACV human ALL model when compared with control mice (10 per group). (D) Cotreatment with ibrutinib and the chemotherapy agents dexamethasone or vincristine synergistically reduced the amount of metabolically active RCH-ACV cells when measured in XTT assays (Fa-CI plot). Combination indices (CI) were calculated on the basis of triplicate measurements using CompuSyn. Left-hand side tables include CIs for the actual experimental points. Right-hand side tables contain CIs for various effective doses of the drug combination, as is indicated. ED, effective dose; Ibr, ibrutinib; Dex, dexamethasone; Vin, vincristine.