Figure 7.
AMG 701 combination treatment with lenalidomide effectively prevented myeloma regrowth in vivo. (A) Head-to-head comparison of AMG 701 and len monotherapy vs combination therapy in the H929 xenograft model in female SCID mice reconstituted with human CD3+ T cells isolated from buffy coats and expanded in vitro. Mice were treated from day 15, when mean tumor volume was 260 mm3 with bolus injections into the peritoneal cavity (vehicle or len) or the lateral tail vein (AMG 701). Control mice reconstituted with or without (w/o) T cells were treated with vehicle once daily from days 15 to 23 (q1dx9). AMG 701 was administered (0.25 mg/kg per administration) once weekly at days 15, 22, 29, 36, and 43; len (0.2 mg/kg per administration) once daily from days 15 to 46 (q1dx32); or both drugs. Eight mice were used in each group, except 5 mice in the vehicle without T-cell group. Values represent mean tumor sizes (mm3) ± SEMs. (B) Symbols indicate individual tumor volumes and lines indicate group mean values ± SDs at days 15, 24, and 43. One-way ANOVA with Tukey multiple comparison test was used for statistics analysis. (C) Using Kaplan-Meier and log-rank analysis, the median overall survival of animals was derived (vehicle, 18 days; vehicle without T cells, 19 days; AMG 701, 38 days; len, 45 days; AMG 701 plus len, >47 days). All 8 mice were alive in the combination therapy group at the end of 47-day follow-up. ***P < .001. n.s., not significant.