Journal
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
Volume 15, Issue 5, Pages 298-302Publisher
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clml.2014.12.005
Keywords
AML; FLT3-ITD; Maintenance; Sorafenib; Stem Cell Transplantation
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We report the successful use of sorafenib after allogeneic hematopoietic cell transplantation (allo-HCT) in 6 patients with FLT3-ITD acute myeloid leukemia (AML). All patients were alive and in complete remission at a median follow-up of 12 months (range, 4-20 months) since initiation of sorafenib. These findings warrant a broader clinical evaluation of the use of maintenance sorafenib in FLT3-ITD AML after allo-HCT. 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. (C) 2015 Elsevier Inc. All rights reserved.
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