Therapeutic dosing with CCX721 reduces myeloma tumor burden. (A) Schematic diagram of the 28-day study with naive syngeneic female C57BL/KaLwRijHsd mice; 18 days after intravenous inoculation with 5TGM-GFP MM cells, establishment of tumors was confirmed by whole-body optical fluorescence imaging, and the mice were then randomized into groups. The groups received either vehicle or CCX721 (100 mg/kg) dosed orally twice a day beginning on day 18; an additional control group received zoledronic acid (120 μg/kg) by subcutaneous injection twice weekly. (B) Serum monoclonal IgG2_bK paraprotein titers from samples taken on day 28 after tumor cell inoculation. (C) Serum IgG2_bK titers from samples taken on days −1, 18, and 28 (mean ± SEM). (D) Representative whole-skeleton fluorescence scans detecting fluorescent myeloma foci in bone, taken on day 28 images (image negatives shown; see supplemental Figure 10 for color originals). OC activity assessed by TRAP staining (red) in the long bones of tumor-bearing mice, representative images using an Olympus BX41 microscope (10× magnification). (E) Histomorphometric analysis of the number of OCs per bone surface. **P < .01 (Mann-Whitney test); ***P < .001 (Mann-Whitney test).