Figure 2.
Effects of venetoclax, dexamethasone, and inotuzumab ozogamicin on ALL PDXs. (A-B) NSG recipients received 1 × 106 P021 cells intravenously. (A-B) Representative BLI results for weeks 0 to 12 after start of treatment (A) and Kaplan-Meier survival curve of recipients treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week and low-dose inotuzumab ozogamicin (10 µg/kg) once per week for 3 weeks as well as triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin) (B). Treatment (6 weeks) started upon engraftment confirmed by BLI 3 weeks after tumor inoculation as indicated (red lines). (C-D) NSG recipients received 1 × 106 P020 cells intravenously. Representative BLI results for weeks 0 to 10 after start of treatment (C) and Kaplan-Meier survival curves of recipients treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week for 6 weeks and low-dose inotuzumab ozogamicin (10 µg/kg) once per week for 3 weeks as well as triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin) (D). Treatment (6 weeks) started upon engraftment confirmed by BLI 3 weeks after tumor inoculation as indicated (red lines). (E-F) High-dose (100 µg/kg) inotuzumab ozogamicin (INOhigh) treatment of NSG mice inoculated with P021 and P020. Representative BLI results for weeks 0 to 45 after start of treatment with high-dose inotuzumab ozogamicin once per week for 3 weeks alone and in combination with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week for 6 weeks. (F) Kaplan-Meier survival curves of inotuzumab ozogamicinhigh (n = 6) (P021, n = 1; P020, n = 5) and venetoclax-dexamethasone-inotuzumab ozogamicinhigh (n = 7) (P021, n = 2; P020, n = 5). All mice treated with venetoclax-dexamethasone-inotuzumab ozogamicinhigh survived the whole investigation period of >50 weeks. (G-H) NSG recipients received 1 × 106 L707 cells intravenously. Tumor proliferation was monitored by noninvasive in vivo BLI based on luciferase reporter expression (G) and overall survival by Kaplan-Meier statistics (H). Representative BLI results for weeks 0 to 11 are shown in panel G. Treatment started upon engraftment confirmed by BLI 2 weeks after tumor inoculation. Recipients were treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) by oral gavage 5 days per week or with inotuzumab ozogamicin (100 µg/kg) intraperitoneally twice a week for 2 weeks or with triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin). Start and end of therapy are indicated by the red lines. Log-rank test was used for statistical survival analyses. *P < .05; **P < .01; ***P < .001.

Effects of venetoclax, dexamethasone, and inotuzumab ozogamicin on ALL PDXs. (A-B) NSG recipients received 1 × 106 P021 cells intravenously. (A-B) Representative BLI results for weeks 0 to 12 after start of treatment (A) and Kaplan-Meier survival curve of recipients treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week and low-dose inotuzumab ozogamicin (10 µg/kg) once per week for 3 weeks as well as triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin) (B). Treatment (6 weeks) started upon engraftment confirmed by BLI 3 weeks after tumor inoculation as indicated (red lines). (C-D) NSG recipients received 1 × 106 P020 cells intravenously. Representative BLI results for weeks 0 to 10 after start of treatment (C) and Kaplan-Meier survival curves of recipients treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week for 6 weeks and low-dose inotuzumab ozogamicin (10 µg/kg) once per week for 3 weeks as well as triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin) (D). Treatment (6 weeks) started upon engraftment confirmed by BLI 3 weeks after tumor inoculation as indicated (red lines). (E-F) High-dose (100 µg/kg) inotuzumab ozogamicin (INOhigh) treatment of NSG mice inoculated with P021 and P020. Representative BLI results for weeks 0 to 45 after start of treatment with high-dose inotuzumab ozogamicin once per week for 3 weeks alone and in combination with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) 5 days per week for 6 weeks. (F) Kaplan-Meier survival curves of inotuzumab ozogamicinhigh (n = 6) (P021, n = 1; P020, n = 5) and venetoclax-dexamethasone-inotuzumab ozogamicinhigh (n = 7) (P021, n = 2; P020, n = 5). All mice treated with venetoclax-dexamethasone-inotuzumab ozogamicinhigh survived the whole investigation period of >50 weeks. (G-H) NSG recipients received 1 × 106 L707 cells intravenously. Tumor proliferation was monitored by noninvasive in vivo BLI based on luciferase reporter expression (G) and overall survival by Kaplan-Meier statistics (H). Representative BLI results for weeks 0 to 11 are shown in panel G. Treatment started upon engraftment confirmed by BLI 2 weeks after tumor inoculation. Recipients were treated with venetoclax (20 mg/kg) and dexamethasone (1 mg/kg) by oral gavage 5 days per week or with inotuzumab ozogamicin (100 µg/kg) intraperitoneally twice a week for 2 weeks or with triple combination therapy (venetoclax-dexamethasone-inotuzumab ozogamicin). Start and end of therapy are indicated by the red lines. Log-rank test was used for statistical survival analyses. *P < .05; **P < .01; ***P < .001.

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