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- Title
Decitabine and Sorafenib Therapy in FLT-3 ITD-Mutant Acute Myeloid Leukemia.
- Authors
Muppidi, Monica R; Portwood, Scott; Griffiths, Elizabeth A; Thompson, James E; Ford, Laurie A; Freyer, Craig W; Wetzler, Meir; Wang, Eunice S
- Abstract
<bold>Background: </bold>Acute myeloid leukemia (AML) characterized by Feline McDonough Sarcoma-like tyrosine kinase-3 (FLT-3) internal tandem duplication (ITD) mutations have poor outcomes. Treatment options are limited, because these mutations confer resistance to conventional chemotherapy. FLT-3 inhibitors such as sorafenib have been studied as a single agent and in combination with conventional chemotherapy or azacytidine with fair responses.<bold>Patients and Methods: </bold>Here we describe our preclinical and clinical experience with the combination of the DNA hypomethylating agent, decitabine and sorafenib for the treatment of FLT-3 ITD-mutant AML.<bold>Results: </bold>In vitro treatment of the human FLT-3 ITD-mutant AML cell line, MV4-11, with both drugs significantly improved growth inhibition over single-agent therapy and resulted in synergistic antitumor effects (combination index < 1). A case series of 6 patients treated with off protocol combination of decitabine and sorafenib demonstrated overall responses in 5 patients (83%) with a median survival of 155 days. Four of the 5 patients (80%) with relapsed/refractory AML achieved complete responses with incomplete count recovery. The combination was also well tolerated.<bold>Conclusion: </bold>Further investigation is warranted to confirm these responses.
- Publication
Clinical Lymphoma, Myeloma & Leukemia, 2015, Vol 15, pS73
- ISSN
2152-2650
- Publication type
journal article
- DOI
10.1016/j.clml.2015.02.033