IMiD pretreatment enhanced potency of AMG 701–induced T cytotoxicity against MM cells, including autologous RRMM patient cell lysis, and mediated synergistic cytotoxicity when added concomitantly. (A-B) T cells from 2 patients were pretreated with len (1 μM), pom (1 μM), or control medium (ctrl) for 4 days; drugs were then washed out before 1-day cocultures with MM cells in the presence of AMG 701 at lower E:T ratios and reduced AMG 701 concentrations. FC analysis was used to evaluate the percentage of MM cell lysis. (A) IMiD-resistant H929(R) (top panel) and RPMI8226 (bottom panel) cells were tested at low concentrations of AMG 701 (top panel) or at lower E:T ratios (1:1, 2:1, 4:1) (bottom panel, AMG 701 of 37.4 pM). (B) BMMCs from 2 RRMM patients were cocultured with len- or pom-pretreated PBMCs (PBMC:BMMC = 5:1) from the same patient to evaluate the percent lysis of autologous patient MM cells. len (C) or pom (D) was added at the same time as AMG 701 in 24-hour cocultures of patient T cells (n = 4) with MM1S (left) or autologous patient CD138⁺ (right) target cells (E:T=5:1). CD138⁺ cells were coincubated with CD138⁻ cells from the same RRMM patients. Values of CI are shown below each graph. CI < 1 indicates synergism of both drugs. All data are shown as the percent lysis (means ± SDs) from multiple independent experiments (A-B, n = 2; C-D, n = 4) in triplicate at each condition. *P < .05; **P < .01; ***P < .001; ****P < .0001.