Figure 4. PRIT synergizes with venetoclax to cure up to 100% of mice bearing B-NHL xenografts.
Mice implanted with subcutaneous xenografts of A. Rec-1 (MCL) or B. U2932 (ABC-DLBCL) were treated with drug diluent only (control), PRIT (CD20-pretargeted RIT using 90Y), venetoclax (daily for 21 days), or PRIT plus venetoclax, when tumors were ~50mm3. A. In Rec-1, our most drug and RT resistant model, single-agent venetoclax (blue) had only marginal effects (p = 0.05 compared to control, Kaplan-Meier log-rank test), and single-agent 800μCi PRIT (purple) induced some remission but all mice died from tumor burden by day 30. Yet combining venetoclax with PRIT (green) produced 75% disease-free survival through day 45 and 38% through day 100 (p = 0.001 for combination group > PRIT group). B. In U2932, single-agent venetoclax (blue) caused complete remission during treatment but no cures, and single-agent 800 and 1200μCi PRIT (purples) cured 10 and 30%, respectively. However combinations of venetoclax with 800 or 1200μCi of PRIT (orange and green, respectively, offset for visual clarity) each cured 100% of mice (p < 0.0006 for either combination group > any single agent group). Cure defined as survival to 120 days with no sign of relapse; synergy defined as survival of the combination group being greater than the additive survival benefits of each agent administered alone (Supplementary Table S1). N = 8–10/group, additional statistics in text.