decitabine + eltrombopag

Decitabine + eltrombopag is an investigational combination therapy consisting of two small molecule drugs with complementary mechanisms. Decitabine is a hypomethylating agent that inhibits DNA methyltransferase, leading to DNA hypomethylation and reactivation of tumor suppressor genes, primarily used in the treatment of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Eltrombopag is an oral thrombopoietin receptor agonist that stimulates megakaryopoiesis and increases platelet counts by activating the thrombopoietin receptor (MPL), commonly used for immune thrombocytopenia and aplastic anemia. The combination has been studied for its synergistic antileukemic effects, particularly in patients with high-risk MDS or AML who are not eligible for intensive chemotherapy. Preclinical studies show enhanced antiproliferative activity, increased cell cycle arrest, and elevated reactive oxygen species–mediated leukemia cell death compared to either agent alone[1][2][3][5]. Clinical trials have explored this regimen to address both cytopenias from decitabine therapy and disease control in advanced MDS/AML.