The optimal schedule of teriflunomide/HMA was more efficacious than the optimal schedule of venetoclax/HMA to treat TP53-mutated complex cytogenetics AML. NSG mice were tail-vein inoculated with 1 × 106 AML cells from a patient with TP53-mutated complex cytogenetics AML. Treatment was started after confirmation of BM engraftment to >10% hCD45+ cells in 3 mice. (A) Experiment schema. (B) Time to distress. Mice were euthanized for signs of distress as per the animal protocol. P values are from log-rank tests. Leukemia burden in the marrow and spleen at time of euthanasia is shown in supplemental Figure 4E-F. (C) Experiment schema for repeat experiment in which all mice were euthanized at a fixed time point (when vehicle-treated mice demonstrated signs of distress at day 81, after 47 days of treatment for all groups). (D) Change in WBC, RBC, and platelet counts between days 13 and 81 (47 days of treatment). (E) BM leukemia burden (percentage of hCD45+ cells) at day 81. Only significant P values (P < .05) are shown, 2-sided Mann-Whitney U test, vs vehicle. (F) Spleen leukemia burden measured by spleen weights at day 81. D, decitabine; Dec, decitabine; Plat, platelet; RBC, red blood cell; Rx, treatment; SC, subcutaneous; T, teriflunomide; Teri, teriflunomide; Veh, vehicle; Ven, venetoclax; WBC, white blood cell.
