Lenalidomide further enhances XmAb5592 induced anti-myeloma activity both in vitro and in vivo. (A) PBMCs were preincubated with or without lenalidomide (2μM) for 48 hours before LDH release-based ADCC assays against target MM cells. Percent specific lysis is shown, as mean ± SD from triplicate measurements. Lenalidomide pretreatment significantly enhanced improved ADCC activity of XmAb5592 than the IgG1 analog. (B) RPMI8226 tumor-bearing mice (n = 5) were treated with PBS, lenalidomide alone, XmAb5592 alone, or XmAb5592 plus lenalidomide. Lenalidomide (25 mg/kg) was injected intraperitoneally twice weekly for 4 doses (▽). XmAb5592 (6 mg/kg) was injected intraperitoneal twice weekly for a total of 8 doses (↓). Combination treatment with XmAb5592 and lenalidomide was more efficacious than either of the treatments alone (day 56 MTV = 46, 127 and 411 mm³ for the combination, XmAb5592 alone and lenalidomide alone, respectively).