An exploratory phase 2 study of investigational Aurora A kinase inhibitor alisertib (MLN8237) in acute myelogenous leukemia and myelodysplastic syndromes

摘要

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 50mg 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. Highlights ? The efficacy and safety of alisertib, an AAK inhibitor, in AML/MDS was evaluated. ? 57 patients received alisertib 50mg twice-daily for 7 days in 21-day cycles. ? The ORR in AML was 17%, with 49% stable disease; no responses were observed in MDS. ? Common AEs included diarrhea, fatigue, nausea, febrile neutropenia, and stomatitis. ? Our results suggest that alisertib has modest single-agent activity in AML.