Sorafenib Maintenance Appears Safe and Improves Clinical Outcomes in FLT3-ITD Acute Myeloid Leukemia After Allogeneic Hematopoietic Cell Transplantation

Clin Lymphoma Myeloma Leuk. 2015 May;15(5):298-302. doi: 10.1016/j.clml.2014.12.005. Epub 2014 Dec 12.


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.

Patients and 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.

Conclusion: 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.

Keywords: AML; FLT3-ITD; Maintenance; Sorafenib; Stem Cell Transplantation.

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Combined Modality Therapy
  • Gene Duplication
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myeloid, Acute / therapy*
  • Maintenance Chemotherapy
  • Male
  • Middle Aged
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Off-Label Use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / therapeutic use*
  • Retrospective Studies
  • Sorafenib
  • Transplantation, Homologous
  • Treatment Outcome
  • fms-Like Tyrosine Kinase 3 / genetics


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3