Journal
DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT
Volume 135, Issue 38, Pages 1852-1856Publisher
GEORG THIEME VERLAG KG
DOI: 10.1055/s-0030-1247870
Keywords
acute myeloid leukemia; AML; FLT3-ITD; receptor tyrosine kinase; allogenic stem cell transplantation; Sorafenib
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Background: The therapeutic options for relapsed or refractory FLT3-ITD positive AML are limited, particularly in case of a prior allogenic stem cell transplantation (SCT) or poor performance status. The clinical value of a targeted intervention using the FLT3-ITD-specific inhibitor sorafenib in this situation is largely unknown. Patients and methods: Between 2007 and 2010 eight patients (4 men, 4 women; age 40-75 years) with relapsed or refractory FLT3-ITD positive acute myeloid leukemia (AML) before (n = 4) and after allogenic SCT (n = 5) were treated off-label with sorafenib. Results: All patients showed rapid hematological responses. There were three complete molecular remissions when sorafenib was given after allogenic SCT. Two of them are ongoing for 12 and 15 months, respectively. Long-term remissions after prior allogenic SCT were associated with the re-establishment of a chronic graft versus host reaction. Side effects could be controlled by dose reduction. Conclusion: Sorafenib is apparently an effective treatment alternative for patients with relapsed or refractory FLT3-ITD positive AML. In the context of a prior allogenic SCT it may have curative potential via inducing a synergism between targeted inhibition of FLT3-ITD and anti-leukemic immunity.
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