ASH 2020 | Therapeutic potential of CPI-482 for AML and post-MPN AML

Raajit Rampal, MD, PhD, Memorial Sloan-Kettering Cancer Center, New York, NY, discusses a study investigating the therapeutic potential of the lysine-specific demethylase 1 (LSD1) inhibitor CPI-482 for treating acute myeloid leukemia (AML) and post-myeloproliferative neoplasm (MPN) AML. CPI-482 administration resulted in significant tumor growth inhibition in SET-2 and HEL 92.1.7 JAK2 mutant AML xenograft mouse models. To further confirm these findings, the research group used a murine model of combined Tp53 loss and Jak2 mutations. Mice were randomized to treatment with vehicle, ruxolitinib, or CPI-482. Results show that treatment with CPI-482 significantly prolonged the survival of mice versus either ruxolitinib or vehicle. Additionally, there was a significant decrease in the spleen size of animals treated with CPI-482 compared to ruxolitinib or vehicle. Finally, it was possible to observe restoration of normal hematopoiesis in the mice treated with CPI-482. This data supports the potential therapeutic impact of the LSD1 inhibitor CPI-482 in AML in the context of the JAK2V617F mutation. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.