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. 2020 May 15;106(4):1034–1046. doi: 10.3324/haematol.2019.244020

Figure 1.

Figure 1.

Venetoclax combined with quizartinib prolongs survival and reduces tumor burden in FLT3-ITD+ xenograft models. NOD/SCID/IL-2Rγnull (NSG) mice were engrafted with luciferase expressing MV4;11 or Molm13 cells and leukemic cell engraftment was confirmed by bioluminescence imaging (BLI) and treatment began 14 days post-inoculation for the MV4;11 model and 7 days post-inoculation in the Molm13 model. Mice were treated orally with 100 mg/kg venetoclax, 2.5 mg/kg or 5 mg/kg quizartinib, or the combination once daily for 21 continuous days and overall survival and disease burden was assessed. (A) Kaplan- Meier survival curve for MV4;11-engrafted mice. N=8-10 animals/group and median survival and statistical significance were determined by log-rank test: *P<0.0001 for venetoclax + 2.5 mg/kg quizartinib vs. 2.5 mg/kg quizartinib; **P<0.0001 for venetoclax + 5 mg/kg quizartinib vs. 5 mg/kg quizartinib. (B) Representative BLI for MV4;11-engrafted mice for each group at indicated time point. (C) Quantitation of the BLI signal from MV4;11-engrafted mice in each group at indicated time post-inoculation: *P<0.0001, P=0.0002, P=0.001 and P=0.0004 for venetoclax + 2.5 mg/kg quizartinib vs. 2.5 mg/kg quizartinib for week 3, 4, 5 and 7, respectively, by unpaired t-test for each time point; **P=0.0004, P=0.0247, P<0.0001 and P=0.0001 for venetoclax + 5 mg/kg quizartinib vs. 5 mg/kg quizartinib for week 3, 4, 7 and 8, respectively, by unpaired t-test for each time point. (D) Kaplan-Meier curve for Molm13-engrafted mice. N=10 animals/group and survival and statistical significance were determined by log-rank test: *P<0.0001 for venetoclax + 2.5 mg/kg quizartinib vs. 2.5 mg/kg quizartinib; **P<0.0001 for venetoclax + 5 mg/kg quizartinib vs. 5 mg/kg quizartinib; and ***P<0.0001 for venetoclax + 5 mg/kg quizartinib vs. venetoclax + 2.5 mg/kg quizartinib. (E) Representative BLI for Molm13-engrafted mice at indicated time point. (F) Quantitation of BLI signal from Molm13-engrafted mice at indicated time point post-inoculation: *P<0.0001, P<0.0001 and P=0.0086 for venetoclax + 2.5 mg/kg quizartinib vs. 2.5 mg/kg quizartinib for week 2, 3 and 4, respectively, by unpaired t test for each timepoint; **P<0.0001 for venetoclax + 5 mg/kg quizartinib vs. 5 mg/kg quizartinib for week 2, 3 and 4 by unpaired t-test for each timepoint; and ***P=0.0129 for venetoclax + 5 mg/kg quizartinib vs. venetoclax + 2.5 mg/kg quizartinib at week 5 by unpaired t-test.