Midostaurin, bortezomib and MEC in relapsed/refractory acute myeloid leukemia
Alison R Walker, Hongyan Wang, Katherine Walsh, Bhavana Bhatnagar, Sumithira Vasu, Ramiro Garzon, Renee Canning, Susan Geyer, Yue-Zhong Wu, Steven M Devine, Rebecca Klisovic, William Blum, Guido Marcucci, Alison R Walker, Hongyan Wang, Katherine Walsh, Bhavana Bhatnagar, Sumithira Vasu, Ramiro Garzon, Renee Canning, Susan Geyer, Yue-Zhong Wu, Steven M Devine, Rebecca Klisovic, William Blum, Guido Marcucci
Abstract
Targeting aberrant tyrosine kinase activity may impact clinical outcome in acute myeloid leukemia (AML). We conducted a phase I study of the tyrosine kinase inhibitor midostaurin with bortezomib alone and in combination with chemotherapy in patients with AML. Patients on dose levels 1 and 2 (DL1 & 2) received midostaurin 50 mg bid and escalating doses of bortezomib (1 to 1.3 mg/m2). Patients on DL3 or higher received midostaurin and bortezomib following chemotherapy with mitoxantrone, etoposide, cytarabine (MEC). None of the patients enrolled to DL1 & 2 had dose-limiting toxicities (DLTs) or a clinical response. Among patients enrolled to DL3 or higher, DLTs were peripheral neuropathy, decrease in ejection fraction and diarrhea. A 56.5% CR rate and 82.5% overall response rate (CR + CR with incomplete neutrophil or platelet count recovery) were observed. The midostaurin/bortezomib/MEC combination is active in refractory/relapsed AML, but is associated with expected drug-related toxicities (NCT01174888).
Keywords: AML; bortezomib; chemotherapy; midostaurin; tyrosine kinase.
Conflict of interest statement
Conflict of Interest: None of the authors report a conflict of interest.
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Source: PubMed