Introduction
myeloid hematologic disorder, AML, MDS or CMML after failure, therapy-related AML, myeloid malignancies
SECONDARY AML, AML, SECONDARY ACUTE MYELOID LEUKEMIA
Secondary acute myeloid leukemia (AML) is a heterogeneous subtype of AML that arises from an antecedent myeloid hematologic disorder or develops after exposure to chemotherapy or irradiation (also called “therapy-related AML”) [Older adults have an higher incidence of secondary AML and other adverse-risk genomic features that are associated with chemoresistance [Pevonedistat is a first-in-class inhibitor of neural cell developmentally downregulated 8 (NEDD8)-activating enzyme (NAE) that catalyzes the rate-limiting step in the process of protein neddylation, a critical step in the degradation of a wide variety of cellular proteins that takes place upstream of the proteasome [Given the established clinical activity of azacitidine plus venetoclax as well as the preclinical and clinical data supporting the use of pevonedistat in myeloid malignancies, we designed a phase 1/2 study to evaluate the triplet combination of azacitidine, venetoclax and pevonedistat in patients with newly diagnosed secondary AML who are unfit for intensive chemotherapy and in patients with MDS or CMML after failure of hypomethylating agents.