Inhibition of AXL by bemcentinib reduces tumor burden and increases survival in an MCL xenograft mouse model. (A) Female nonobese diabetic severe combined immunodeficiency gamma mice were injected IV with 5 × 10⁵ JeKo-1^Luc+ cells. The mice were imaged weekly, both dorsally and ventrally (10 minutes after intraperitoneal injection with 150 mg/kg of 25 mg/mL D-luciferin). The mice were distributed in the following groups: control (vehicle only every day), bemcentinib treatment (50 mg/kg twice a day), ibrutinib treatment (25 mg/kg every day), and combination treatment (ibrutinib + bemcentinib) based on total bioluminescence. Following the assignment, there was no statistical difference between the groups (P > .99; 1-way analysis of variance test). JeKo-1^Luc+ xenografts were treated for 4 weeks with vehicle every day (control), ibrutinib (25 mg/kg, every day), bemcentinib (50 mg/kg, twice a day) or the combination of ibrutinib and bemcentinib (same dose as single treatment) (n = 6). (B) Bioluminescence imaging (BLI) was assessed weekly to monitor disease progression. (C) Quantification of BLI signal from the different treatment groups in week 3 (n = 6). Bemcentinib significantly reduced the BLI signal in comparison with the control group (P < .0004) or to ibrutinib single treatment (P < .0247). (D) Kaplan-Meier plots showing the effect of the different treatments on the survival of mice with MCL-cell xenografts (n = 8).