In vivo efficacy of daratumumab in ETP T-ALL and non-ETP T-ALL. PDX models were treated with isotype control or daratumumab weekly for 3 to 8 weeks depending on the rate of leukemia progression in control animals. Experiments were also varied based on daratumumab treatment at “low” vs “high” disease burden. The mice were treated an average of 4 doses at the high disease burden and 7 at low disease burden. The duration of treatment was determined by the need to euthanize control animals because of overwhelming disease burden. Each experiment represents n = 5 mice per treatment group. (A) Trials of mice treated at high disease burden that did not experience toxicity are shown for T-ALL and ETP T-ALL xenografts. (Left) Histogram of CD38-PE (red) with the corresponding MFI compared with an unstained (blue) and isotype control (green) to demonstrate positivity above background. Graphed are means and standard deviations of absolute blast count on the vertical axis and weeks of treatment on the horizontal axis. Treatment groups (red) were compared with mice treated with isotype antibody control (blue) for each PDX model using a nonparametric Mann-Whitney U test. P values are shown. ID-TALL33 was only bled once at the time of harvest because of the aggressiveness of disease progression. Mice engrafted from this sample do not tolerate serial bleeds; therefore, blood and spleen data are shown only at the time euthanization. (B) Experiments performed at low disease burden of samples that experienced toxicity when tested at high disease burden. Two samples, ID-TALL8 and ID-ETP12, represent repeated trials of daratumumab tested at low disease state; they did not respond at the high disease state.