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

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

Author information

1
Department of Internal Medicine/Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
2
Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
3
Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon.
4
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.

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.

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

PMID:
25550214
DOI:
10.1016/j.clml.2014.12.005
[Indexed for MEDLINE]

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