Submitted March 2, 2009
Accepted April 16, 2009
Compassionate-use of sorafenib in Flt3-ITD positive acute myeloid leukemia: sustained regression prior and post allogenic stem cell transplantation
Stephan Metzelder, Ying Wang, Ellen Wollmer, Michael Wanzel, Sabine Teichler, Anuhar Chaturvedi, Martin Eilers, Erich Enghofer, Andreas Neubauer, and Andreas Burchert*
Philipps University of Marburg, Medical Center of the University Giessen and Marburg, Campus Marburg, Department of Hematology, Oncology and Immunology, Marburg, Germany
Institute for Molecular Biology and Tumor Research (IMT), Marburg, Germany
Department of Physiological Chemistry, Biocenter, Universitat Wurzburg, Wurzburg, Germany
Bayer Schering Pharma, BU Oncology, Leverkusen, Germany
* Corresponding author; email: burchert{at}staff.uni-marburg.de.
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 multi-kinase-, 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 six patients treated either prior (n=2), post (n=3), or both, prior and post (n=1) allogenic stem cell transplantation (allo-SCT). Sorafenib-induced remissions facilitated allo-SCT in two of the three refractory patients. Two of the four patients that were treated after allo-SCT survived 216 and 221 days, respectively, while the other two remain in ongoing complete molecular remission. Sorafenib-response was associated with an inhibition of the anti-apoptotic Flt3-ITD target Stat-5 in vivo.
Together, sorafenib-monotherapy prior or post allo-SCT has remarkable clinical activity in poor risk Flt3-ITD-positive AML and deserves further evaluation in prospective clinical trials.
