Midostaurin, bortezomib and MEC in relapsed/refractory acute myeloid leukemia

Leukemia & Lymphoma
Alison R WalkerGuido 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).

References

Dec 16, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards
May 27, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jorge CortesHagop Kantarjian
Apr 14, 2010·Cancer Cell·Shujun LiuGuido Marcucci
Jan 12, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guido MarcucciHartmut Döhner
Jan 1, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Guido MarcucciClara D Bloomfield
Sep 17, 2015·The New England Journal of Medicine·Hartmut DöhnerClara D Bloomfield

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Citations

Sep 30, 2017·Expert Review of Clinical Pharmacology·Sabine KayserRichard F Schlenk
Oct 21, 2017·Therapeutic Advances in Hematology·Molly M GalloglyBrenda W Cooper
Oct 27, 2017·Cancer Metastasis Reviews·Jacqueline CloosGerrit Jansen
Oct 5, 2017·Pharmacotherapy·Lindsay C Stansfield, Daniel A Pollyea
Jun 15, 2017·Future Oncology·Mrinal M Patnaik
Dec 7, 2018·Hematology·Laura C Michaelis
Jan 18, 2019·Leukemia & Lymphoma·Jan Philipp BewersdorfAmer M Zeidan
Jun 25, 2019·Expert Review of Hematology·Eran Tallis, Gautam Borthakur
Oct 30, 2019·Mini Reviews in Medicinal Chemistry·Xu HuDahong Li
Sep 19, 2019·Biomarker Research·Juanjuan ZhaoDelong Liu
Dec 6, 2018·Journal of Hematology & Oncology·Mei WuXiongpeng Zhu
Aug 10, 2018·JCI Insight·Irum KhanAndrei L Gartel
Apr 18, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anjali S AdvaniMikkael A Sekeres
Jan 12, 2021·Frontiers in Oncology·Vanessa E Kennedy, Catherine C Smith

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