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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).
Acknowledgements
Midostaurin and bortezomib were provided by Novartis Pharmaceuticals and Millennium, respectively.
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1135435.
Financial support for this study was provided by Novartis Pharmaceuticals.
This work was supported in part by the National Cancer Institute Grants No. CA101140 (GM), CA102031 (GM), CA140158 (GM, WB, AW), K12CA133250 (AW). AW is a scholar of the American Society of Hematology-Harold Amos Medical Faculty Development Program.