Figure 4. MLN8237 plus Vincristine plus Rituximab is synthetic lethal and curative in a mouse xenograft model of MCL.


(A). Granta-519 xenograft mice (n=12 per cohort) were treated with saline (control), M 30 mg/kg + R 10 mg/kg, M 30 mg/kg + V 0.375 mg/kg and M 30 mg/kg + V 0.375 mg/kg + R 10 mg/kg. MLN8237 was given by PO Q1D × 3 weeks, vincristine and rituximab by IV Q1W × 4 weeks. MV1 represents the phase of tumor regression while MV2 represents the phase of lymphoma relapse. Tumor burdens were measured, graphed and represented as mean ± S.E.M. (B). Kaplan-Meier survival curves show overall survival differences between MVR in comparison to control, MR and MV.