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
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
Externí odkaz: