Aurora Kinase A Inhibition Provides Clinical Benefit, Normalizes Megakaryocytes, and Reduces Bone Marrow Fibrosis in Patients with Myelofibrosis: A Phase I Trial.
Naseema GangatChristian MarinaccioRonan SwordsJustin M WattsSandeep GurbuxaniAlfred RademakerAngela J FoughtOlga FrankfurtJessica K AltmanQiang Jeremy WenNoushin FarnoudChristopher A FamulareAkshar PatelRoberto TapiaRangit R VallapureddyStephanie BarathAmy GrafAmy HandlogtenDarci ZblewskiMrinal M PatnaikAref Al-KaliYvonne Trang DinhKristen Englund PrahlShradha PatelJuan Carlos NobregaDalissa TejeraAmber ThomassenJuehua GaoPeng JiRaajit K RampalFrancis J GilesAyalew TefferiBrady SteinJohn D CrispinoPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2019)
Given the limitations of ruxolitinib, novel therapies are needed for myelofibrosis. In this study, alisertib provided clinical benefit and exhibited the expected on-target effect on the megakaryocyte lineage, resulting in normalization of these cells and reduced fibrosis in the majority of patients for which sequential marrows were available. Thus, AURKA inhibition should be further developed as a therapeutic option in myelofibrosis.See related commentary by Piszczatowski and Steidl, p. 4868.