Phase II study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation
Mené sur 40 patients atteints d'une leucémie myéloïde aiguë présentant une mutation FLT3-ITD, cet essai de phase II évalue l'efficacité d'un traitement combinant le sorafenib et un agent déméthylant, la 5-azacytidine
We examined the efficacy of combining sorafenib and 5-azacytidine (AZA) in patients with AML and the FLT3-ITD mutation. Patients received AZA 75 mg/m2 IV daily for 7 days and sorafenib 400 mg PO twice daily continuously; cycles were repeated at approximately one month intervals. Forty-three AML patients with a median age of 64 years (range, 24-87) were enrolled; 37 were evaluable for response. The FLT-3-ITD mutation was detected in 40 (93%) patients with a median allelic ratio of 0.28 (range, 0 - 0.93). They had received a median of 2 prior treatment regimens (range, 0-7); 9 had failed prior therapy with a FLT3 kinase inhibitor. The response rate was 46%, including 10 (27%) CRi, 6 (16%) CR, and 1 (3%) PR. The median time to achieve CR/CRi was 2 cycles (Range, 1 - 4), and the median duration of CR/CRi was 2.3 months (Range, 1 - 14.3 months). 64% of patients achieved adequate (defined as >85%) FLT3 inhibition during their first cycle of therapy. The degree of FLT3 inhibition correlated with plasma sorafenib concentrations. FL levels did not rise to levels seen in prior studies of patients receiving cytotoxic chemotherapy. The combination of AZA and sorafenib is effective for patients with relapsed AML and the FLT-3-ITD mutation. (The study was registered on ClinicalTrials.gov as NCT01254890.)