Page 96 - Haematologica Vol. 110 - January 2025

ARTICLE - LP-118: a promising treatment for CLL J. Ravikrishnan et al. AB
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Figure 6. LP-118 decreases tumor size in RS4;11 xenograft and improves survival in OSU-chronic lymphocytic leukemia xenograft models. (A) NOG mice were engrafted with RS4;11 wild-type (WT) BCL2 cells and monitored for tumor volume. Data were cubic root transformed to minimize variance. Mixed effect model was used to compare tumor sizes among groups (**0.01≥P≥0.001, ****P≤0.0001). (B) Survival curve of NOG mice engrafted with RS4;11 WT BCL2 and treated with vehicle, venetoclax (6.25 mg/kg), or LP-118 (6.25 mg/kg). Log-rank Mantel-Cox test was performed (***P≤0.0002). (C) NOG mice were engrafted with RS4;11 cells overexpressing G101V mutant BCL2 (G101VOE), treated with vehicle, venetoclax (100 mg/kg), or LP-118 (50, 100 or 150 mg/kg), and monitored for tumor volume. Data were cubic root transformed to minimize variance. Mixed effect model was used to compare tumor sizes among groups (*0.05≥P>0.01, **0.01≥P≥0.001, ***P<0.001). (D) Survival curve of NOG mice engrafted with RS4;11 G101VOE BCL2 and treated with vehicle, venetoclax (100 mg/kg), or LP-118 (50, 100 or 150 mg/kg). Gehan-Breslow-Wilcoxon test was performed (*0.05≥P>0.01, **0.01≥P≥0.001, ***P<0.001). (E) NOG mice were engrafted with OSU-CLL and monitored for sur- vival until the endpoint of hind limb paralysis. Log-rank Mantel-Cox test was performed. (F) Complete blood cell (CBC) count of OSU-CLL engrafted NOG mice were used to determine platelet counts. Mixed effect model was used to compare among groups. NS: not significant, *0.05≥P>0.01, **0.01≥P≥0.001, ***P<0.001. Ven: venetoclax; LP: LP-118.
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