Comparative dose-response effects of CD38-bispecific PRIT vs CD38-SA PRIT on tumor growth and survival of mice bearing CD38+BL xenografts. This figure presents data from 2 replicate experiments, each using 8 to 10 athymic nude mice per group. In total, n = 18 mice per treatment were injected at −24 hours with a pretargeting protein (CD38 bispecific, CD38-SA, or control [anti-CD20] bispecific), then at −1 hour with CA, and at 0 hours with 600 or 1000 µCi 90Y-DOTA–biotin. An additional n = 10 mice per group received only pretargeting protein (CD38 bispecific or CD38-SA) and CA, with no 90Y-DOTA–biotin. (A) All control mice including untreated (black), pretargeting protein without 90Y (maroon and navy), and control bispecific 1000-µCi groups (gray) experienced rapid tumor progression and died by day 14. All CD38 PRIT mice showed CR by day 11, and subsequent strongly reduced tumor progression relative to controls (P < .0001, any CD38 PRIT group vs any control group). However, CD38-bispecific PRIT (reds) outperformed CD38-SA PRIT (blues), the former showing later and fewer tumor progressions in the 600- and 1000-µCi treatment groups (P < .003, CD38 bispecific vs CD38-SA). (B) Kaplan-Meier survival analyses reflect the tumor volume results, showing greatly improved survival in each CD38 PRIT group relative to each control (P < .0001), and improved survival of CD38-bispecific PRIT mice relative to CD38-SA PRIT mice, across 600- and 1000-µCi levels (P < .004, CD38 bispecific vs CD38-SA).