TY - JOUR
T1 - Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
AU - Levis, Mark
AU - Ravandi, Farhad
AU - Wang, Eunice S.
AU - Baer, Maria R.
AU - Perl, Alexander
AU - Coutre, Steven
AU - Erba, Harry
AU - Stuart, Robert K.
AU - Baccarani, Michele
AU - Cripe, Larry D.
AU - Tallman, Martin S.
AU - Meloni, Giovanna
AU - Godley, Lucy A.
AU - Langston, Amelia A.
AU - Amadori, Sergio
AU - Lewis, Ian D.
AU - Nagler, Arnon
AU - Stone, Richard
AU - Yee, Karen
AU - Advani, Anjali
AU - Douer, Dan
AU - Wiktor-Jedrzejczak, W.
AU - Juliusson, Gunnar
AU - Litzow, Mark R.
AU - Petersdorf, Stephen
AU - Sanz, Miguel
AU - Kantarjian, Hagop M.
AU - Sato, Takashi
AU - Tremmel, Lothar
AU - Bensen-Kennedy, Debra M.
AU - Small, Donald
AU - Smith, B. Douglas
PY - 2011/3/24
Y1 - 2011/3/24
N2 - In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.
AB - In a randomized trial of therapy for FMS-like tyrosine kinase-3 (FLT3) mutant acute myeloid leukemia in first relapse, 224 patients received chemotherapy alone or followed by 80 mg of the FLT3 inhibitor lestaurtinib twice daily. Endpoints included complete remission or complete remission with incomplete platelet recovery (CR/CRp), overall survival, safety, and tolerability. Correlative studies included pharmacokinetics and analysis of in vivo FLT3 inhibition. There were 29 patients with CR/CRp in the lestaurtinib arm and 23 in the control arm (26% vs 21%; P = .35), and no difference in overall survival between the 2 arms. There was evidence of toxicity in the lestaurtinib-treated patients, particularly those with plasma levels in excess of 20μM. In the lestaurtinib arm, FLT3 inhibition was highly correlated with remission rate, but target inhibition on day 15 was achieved in only 58% of patients receiving lestaurtinib. Given that such a small proportion of patients on this trial achieved sustained FLT3 inhibition in vivo, any conclusions regarding the efficacy of combining FLT3 inhibition with chemotherapy are limited. Overall, lestaurtinib treatment after chemotherapy did not increase response rates or prolong survival of patients with FLT3 mutant acute myeloid leukemia in first relapse. This study is registered at www.clinicaltrials.gov as #NCT00079482.
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U2 - 10.1182/blood-2010-08-301796
DO - 10.1182/blood-2010-08-301796
M3 - Article
C2 - 21270442
AN - SCOPUS:79953124734
SN - 0006-4971
VL - 117
SP - 3294
EP - 3301
JO - Blood
JF - Blood
IS - 12
ER -