Introduction
AML
ACUTE MYELOID LEUKEMIA, AML
Despite recent advances, effective and well-tolerable treatment options for patients with acute myeloid leukemia (AML) who are ineligible to receive intensive chemotherapy remain limited. Hypomethylating agents (HMA; e.g., azacitidine and decitabine) and low-dose cytarabine (LDAC) are increasingly being used as backbones for combination therapies with novel drugs. Venetoclax and glasdegib are two examples of molecularly targeted combination partners which have provided improved outcomes compared to HMA or LDAC monotherapies, but overall survival (OS) remains modest [Nintedanib is a potent, orally available, small molecule triple tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF) receptor VEGFR-1/-2/-3, fibroblast growth factor (FGF) receptor FGFR-1/-2/-3 and platelet derived growth factor (PDGF) receptor PDGFR-α/-β signaling [In order to translate these preclinical findings, we investigated the safety and efficacy of nintedanib added to LDAC in a phase 1/2 study in patients 60 years or older with untreated or relapsed/refractory (r/r) AML ineligible for intensive chemotherapy. The results of the dose-finding phase 1 part have been previously published and suggested a continuation of the trial with a phase 2 recommended dose (P2RD) of 200 mg nintedanib twice daily in combination with LDAC [