A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs)
Key claim: A phase II randomized trial is evaluating whether ASTX727 (oral cedazuridine-decitabine) combined with iadademstat (an LSD1 inhibitor) is more effective than ASTX727 alone in patients with accelerated or blast phase Philadelphia chromosome-negative MPNs.
Abstract
This phase II trial compares the effect of ASTX727 in combination with iadademstat to ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). ASTX727 is a combination of two drugs, cedazuridine and decitabine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ASTX727 in combination with iadademstat may be more effective than ASTX727 alone in treating patients with accelerated or blast phase Philadelphia chromosome negative MPNs.
Why this matters
Accelerated and blast-phase transformation is the convergent terminal pathway across PMF, PV, and ET, and historically carries the worst prognosis with no standard of care. A randomized trial of an oral HMA (ASTX727) ± LSD1 inhibition (iadademstat) is notable because it is the first head-to-head test of an epigenetic combination for this transformation phenotype, potentially reshaping subtype-specific transformation management.