Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation
Autor: | Sabine Teichler, Erich Enghofer, Martin Eilers, Andreas Neubauer, Anuhar Chaturvedi, Andreas Burchert, Michael Wanzel, S K Metzelder, Ellen Wollmer, Ying Wang |
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Rok vydání: | 2009 |
Předmět: |
Male
Oncology Pyridines medicine.medical_treatment Hematopoietic stem cell transplantation Biochemistry Tyrosine-kinase inhibitor hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols Medicine Benzenesulfonates Remission Induction Hematopoietic Stem Cell Transplantation Myeloid leukemia Hematology Middle Aged Sorafenib Combined Modality Therapy Neoplasm Proteins Leukemia Treatment Outcome Leukemia Myeloid Tandem Repeat Sequences Acute Disease Female Stem cell psychological phenomena and processes medicine.drug Adult Niacinamide medicine.medical_specialty medicine.drug_class Immunology Antineoplastic Agents Internal medicine Correspondence Humans Transplantation Homologous Protein Kinase Inhibitors neoplasms business.industry Phenylurea Compounds Cancer Cell Biology medicine.disease Transplantation fms-Like Tyrosine Kinase 3 Drug Resistance Neoplasm Drug Evaluation business |
Zdroj: | Blood. 113:6567-6571 |
ISSN: | 1528-0020 0006-4971 |
Popis: | Acute myeloid leukemia (AML) patients with internal tandem duplication (ITD) mutations in the Fms-like tyrosine-3 (FLT3) gene have a dismal prognosis. Here we report compassionate-use results with the multikinase and FLT3-ITD inhibitor sorafenib for the treatment of relapsed or refractory FLT3-ITD–positive AML. Sorafenib induced clinically meaningful and very rapid responses in all 6 patients treated either before (n = 2), after (n = 3), or both before and after (n = 1) allogeneic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in 2 of the 3 refractory patients. Two of the 4 patients who were treated after allo-SCT survived 216 and 221 days, respectively, whereas the other 2 remain in ongoing complete molecular remission. Sorafenib response was associated with an inhibition of the antiapoptotic FLT3-ITD target Stat-5 in vivo. Together, sorafenib monotherapy before or after allo-SCT has remarkable clinical activity in poor risk FLT3-ITD–positive AML and deserves further evaluation in prospective clinical trials. |
Databáze: | OpenAIRE |
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