title: Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation.
abstract: BACKGROUND
  The FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) gene is one of the most frequently observed genetic alterations in acute myeloid leukemia (AML), with an incidence of about 20% to 30%. FLT3-ITD is significantly associated with a poor outcome, and offering an allogeneic hematopoietic cell transplantation (allo-HCT) is recommended for patients harboring this mutation. Sorafenib is a tyrosine kinase inhibitor active against RAF, VEGF, and FLT3-ITD. It has been used in an off-label fashion in FLT3-ITD AML.
  
  
  METHODS
  We retrospectively assessed the successful use of sorafenib after allo-HCT in patients with FLT3-ITD AML. Six FLT3-ITD AML patients received sorafenib as posttransplantation maintenance therapy (n = 5) or as salvage therapy after a post-allo-HCT relapse (n = 1) and continued afterward.
  
  
  RESULTS
  One patient developed myocardial infarction 100 days after initiation of sorafenib. Interestingly, skin graft versus host disease (grade II) was observed in 5 of 6 patients and generally occurred within few days after initiation of sorafenib, but it responded promptly to corticosteroid therapy in all patients. All 6 patients were alive and in complete remission at a median follow-up of 16 months (range, 10-29 months) since first induction and at a median follow-up of 12 months (range, 4-20 months) since initiation of sorafenib. Remarkably, the disease of all patients was in molecular remission.
  
  
  CONCLUSIONS
  Sorafenib appears to be an effective maintenance therapy after allo-HCT in FLT3-ITD AML, with achievement of durable complete responses. This suggests an immunomodulatory effect of sorafenib in the posttransplantation setting and warrants a broader clinical evaluation of the use of maintenance sorafenib in FLT3-ITD AML.
authors.affiliation: Department of Internal Medicine/Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Antar
authors.affiliation: Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Kharfan-Dabaja
authors.affiliation: Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Rami
authors.initials: R
authors.lastname: Mahfouz
authors.affiliation: Department of Internal Medicine/Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon; Department of Cell Biology, Anatomy and Physiological Sciences, American University of Beirut, Beirut, Lebanon. Electronic address: bazarbac@aub.edu.lb.
authors.forename: Ali
authors.initials: A
authors.lastname: Bazarbachi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D020440:Gene Duplication; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D056687:Off-Label Use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: AML; FLT3-ITD; Maintenance; Sorafenib; Stem Cell Transplantation