Figure 4.

CC-92480 induces tumor regression and extends survival in TCL models in vivo. (A) Workflow of ALCL SUP-M2 in vivo model. (B) Tumor volume of mice treated with vehicle, 3 mg/kg pomalidomide (pom), or 1 mg/kg CC-92480 by mouth daily (n = 3 per arm). (C) Workflow of AITL model using DFTL-78024 PDX cells. (D) Western blot analysis of IKZF1 and ZFP91 expression in DFTL-78024 PDX cells upon exposure to lenalidomide (len), pom, or CC-92480 at indicated doses for 24 hours. (E) Spleens were harvested from mice treated with vehicle (n = 3), pom (3 mg/kg, n = 4), CC-92480 (1 mg/kg, n = 4), as well as from unengrafted NSG mice (normal, n = 3). Spleen/body weight, spleen tumor burden (the number of Annexin V-PI- tumor cells), and the percent of Annexin V⁺ tumor cells are shown on the right. Data are presented as mean plus or minus SEM. (F) Workflow of ATLL model using DFTL-69579 PDX cells. (G) Representative ultrasounds showing reduced spleen size (dotted border) after 10-day treatment with CC-92480. (H) Kaplan-Meier survival analyses by log-rank test after 21-day treatment with vehicle (n = 5), pom (3 mg/kg, n = 4), or CC-92480 (1 mg/kg, n = 5). (I) Workflow of T-cell prolymphocytic leukemia model using DFTL-28776 PDX cells that express a luciferase reporter. (J) Bioluminescence imaging of mice exposed to vehicle (n = 5), pomalidomide (3 mg/kg, n = 5), or CC-92480 (1 mg/kg, n = 5) for 21 days. (K) Kaplan-Meier survival analyses by log-rank test. Arrows indicate start (day 0) and stop (day 21) of treatment. *P < .05; **P < .01; ***P < .001. NSG, NOD scid gamma; SEM, standard error of the mean.