title: An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes.
abstract: Alisertib (MLN8237) is an investigational, oral, selective, Aurora A kinase (AAK) inhibitor. In this phase 2 trial, 57 patients with acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome received alisertib 50 mg BID for 7 days in 21-day cycles. Responses in 6/35 AML patients (17% response rate with an additional 49% stable disease, 34% transfusion independence) included 1 complete response lasting >1 year. No responses were observed in MDS patients. Adverse events >30% included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. Results suggest modest activity in AML, supporting further research to better understand how AAK inhibition may induce leukemic cell senescence.
authors: John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
authors: Stuart L
authors: SL
authors: Goldberg
authors: Service d׳hématologie Clinique, Hôpital Avicenne (AP-HP)/Université, Paris 13, Bobigny, France.
authors: Pierre
authors: P
authors: Fenaux
authors: Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV, USA.
authors: Michael D
authors: MD
authors: Craig
authors: Service d׳hématologie et Thérapie Cellulaire, CNRS UMR 7292, CHRU de Tours, France.
authors: Emmanuel
authors: E
authors: Gyan
authors: Division of Hematology and Cellular Therapy, Western Pennsylvania Cancer Institute, Pittsburgh, PA, USA.
authors: John
authors: J
authors: Lister
authors: Hôpital Maisonneuve-Rosemont, Montreal, QC, Canada.
authors: Jeannine
authors: J
authors: Kassis
authors: Service d׳hématologie CHU Bordeaux, Pessac, France.
authors: Arnaud
authors: A
authors: Pigneux
authors: David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors: Gary J
authors: GJ
authors: Schiller
authors: Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors: JungAh
authors: J
authors: Jung
authors: Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors: E
authors: E
authors: Jane Leonard
authors: Takeda Pharmaceuticals International Co., Cambridge, MA, USA.
authors: Howard
authors: H
authors: Fingert
authors: Division of Oncology, Washington University Medical School, St. Louis, MO, USA.
authors: Peter
authors: P
authors: Westervelt
keywords: Acute myeloid leukemia (AML); Alisertib; Aurora A kinase inhibitor; Myelodysplastic syndrome (MDS); Safety