TY - JOUR
T1 - Phase 2 study of azacytidine plus sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem duplication mutation
AU - Ravandi, Farhad
AU - Alattar, Mona Lisa
AU - Grunwald, Michael R.
AU - Rudek, Michelle A.
AU - Rajkhowa, Trivikram
AU - Richie, Mary Ann
AU - Pierce, Sherry
AU - Daver, Naval
AU - Garcia-Manero, Guillermo
AU - Faderl, Stefan
AU - Nazha, Aziz
AU - Konopleva, Marina
AU - Borthakur, Gautam
AU - Burger, Jan
AU - Kadia, Tapan
AU - Dellasala, Sara
AU - Andreeff, Michael
AU - Cortes, Jorge
AU - Kantarjian, Hagop
AU - Levis, Mark
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013/6/6
Y1 - 2013/6/6
N2 - Patients received 5-azacytidine (AZA) 75 mg/m2 intravenously daily for 7 days and sorafenib 400 mg orally twice daily continuously; cycles were repeated at ∼1-month intervals. Forty-three acute myeloid leukemia (AML) patients with a median age of 64 years (range, 24-87 years) were enrolled; 37 were evaluable for response. FMS-like tyrosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation was detected in 40 (93%) patients, with a median allelic ratio of 0.32 (range, 0.009-0.93). 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%) complete response with incomplete count recovery (CRi), 6 (16%) complete responses (CR), and 1 (3%) partial response. 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). Sixty-four percent 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. FLT3 ligand 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 relapsedAMLand FLT-3-ITD. This trial was registered at clinicaltrials.gov as#NCT01254890. (Blood. 2013;121(23): 4655-4662).
AB - Patients received 5-azacytidine (AZA) 75 mg/m2 intravenously daily for 7 days and sorafenib 400 mg orally twice daily continuously; cycles were repeated at ∼1-month intervals. Forty-three acute myeloid leukemia (AML) patients with a median age of 64 years (range, 24-87 years) were enrolled; 37 were evaluable for response. FMS-like tyrosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation was detected in 40 (93%) patients, with a median allelic ratio of 0.32 (range, 0.009-0.93). 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%) complete response with incomplete count recovery (CRi), 6 (16%) complete responses (CR), and 1 (3%) partial response. 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). Sixty-four percent 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. FLT3 ligand 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 relapsedAMLand FLT-3-ITD. This trial was registered at clinicaltrials.gov as#NCT01254890. (Blood. 2013;121(23): 4655-4662).
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U2 - 10.1182/blood-2013-01-480228
DO - 10.1182/blood-2013-01-480228
M3 - Article
C2 - 23613521
AN - SCOPUS:84881035623
SN - 0006-4971
VL - 121
SP - 4655
EP - 4662
JO - Blood
JF - Blood
IS - 23
ER -