Figure 4.

PF-06747143 greatly reduces BM tumor burden as a monotherapy and in combination with SOCs in a disseminated MM model. OPM-2-Luc MM cells were implanted IV (5 × 10⁶ cells) and allowed to spontaneously migrate and home in the BM for 8 days, when animals were randomized based on luciferase activity detected in the large bones (n = 10 per group). Animals showing hind leg paralysis were euthanized, and this was the survival end point of the study. (A) Treatment schematic representation. Animals were treated with 10 mg/kg of IgG1 control and PF-06747143 Ab’s, subcutaneously, weekly, for 5 doses. Melphalan was dosed 1 mg/kg, intraperitoneally (IP), twice a week, for a total of 4 cycles. (B) Tumor burden was determined by bioluminescence imaging and quantification. Data points represent the mean bioluminescence ± SEM. (C) Whole body bioluminescence representative imaging showing tumor burden in n = 5 mice per group over time. (D) Kaplan-Meier survival curve. (E) Treatment schematic representation. Animals were treated with 1 mg/kg of IgG1 control and PF-06747143 Ab’s, subcutaneously, weekly, for a total of 7 doses. Bortezomib was dosed at 0.5 mg/kg, administered IP, 2 times per week, for a total of 4 cycles. (F) Tumor burden was determined by bioluminescence imaging quantification. Data points represent the mean bioluminescence ± SEM. (G) Whole body bioluminescence representative images showing tumor burden in n = 5 mice per group over time. (H) Kaplan-Meier survival curve.