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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)2100-2108
Number of pages9
JournalLeukemia and Lymphoma
Volume57
Issue number9
DOIs
StatePublished - Sep 1 2016

Keywords

  • AML
  • bortezomib
  • chemotherapy
  • midostaurin
  • tyrosine kinase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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