Figure 2. Birinapant exhibits significant single-agent efficacy against Ph-like BCP-ALL PDXs in vivo.

(A) individual %huCD45⁺ cells in the peripheral blood over time (top panels) and Kaplan–Meier curves for EFS (bottom panels) for mice engrafted with 3 Ph-like BCP-ALL PDXs. Vehicle controls, dashed lines; birinapant treated (30 mg/kg), red solid lines. Black boxes on the x-axis indicate treatment days. (B) distributions of objective response measures (ORMs) of individual mice from 19 PDX lines treated with birinapant. (C) Midpoint difference representation of the median objective response scores in mice engrafted with ALL PDXs and treated with birinapant. A score of -5 to 0 indicates that an objective response was not achieved for a given xenograft; whereas a score of > 0 to 5 indicates an objective response. Red bars indicate treatments for which the EFS is significantly different between control and treated mice, blue bars indicate no statistical difference in EFS. (D) In vivo birinapant efficacy stratified according to xenograft ALL subtype and quantified by median EFS T-C values. (E) In vivo birinapant efficacy stratified according to PDX ALL subtype and quantified by median EFS T/C values. (F) Correlation of in vitro and in vivo response as determined by T-C. Regression line and 95% confidence intervals are shown. (G) Groups of 3 mice engrafted with PDXs ALL-2 or ALL-7 were treated with birinapant (30 mg/kg) or vehicle control and euthanized 6 h later. Lysates were prepared from spleen-derived cells (>95% huCD45⁺) and immunoblotted for cIAP1 and downstream signaling proteins. Each lane represents one mouse.