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Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse

Levis, Mark; Ravandi, Farhad; Wang, Eunice S.; Baer, Maria R.; Perl, Alexander; Coutre, Steven; Erba, Harry; Stuart, Robert K.; Baccarani, Michele and Cripe, Larry D., et al. (2011) In Blood 117(12). p.3294-3301
Abstract
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... (More)
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 20 mu M. 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. (Blood. 2011;117(12): 3294-3301) (Less)
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Blood
volume
117
issue
12
pages
3294 - 3301
publisher
American Society of Hematology
external identifiers
  • wos:000288848500012
  • scopus:79953124734
ISSN
1528-0020
DOI
10.1182/blood-2010-08-301796
language
English
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yes
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a8f7bf8b-20e4-4369-8a8e-9e9855514e45 (old id 1926127)
date added to LUP
2011-05-02 08:30:48
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2017-11-19 03:04:26
@article{a8f7bf8b-20e4-4369-8a8e-9e9855514e45,
  abstract     = {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 20 mu M. 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. (Blood. 2011;117(12): 3294-3301)},
  author       = {Levis, Mark and Ravandi, Farhad and Wang, Eunice S. and Baer, Maria R. and Perl, Alexander and Coutre, Steven and Erba, Harry and Stuart, Robert K. and Baccarani, Michele and Cripe, Larry D. and Tallman, Martin S. and Meloni, Giovanna and Godley, Lucy A. and Langston, Amelia A. and Amadori, Sergio and Lewis, Ian D. and Nagler, Arnon and Stone, Richard and Yee, Karen and Advani, Anjali and Douer, Dan and Wiktor-Jedrzejczak, W. and Juliusson, Gunnar and Litzow, Mark R. and Petersdorf, Stephen and Sanz, Miguel and Kantarjian, Hagop M. and Sato, Takashi and Tremmel, Lothar and Bensen-Kennedy, Debra M. and Small, Donald and Smith, B. Douglas},
  issn         = {1528-0020},
  language     = {eng},
  number       = {12},
  pages        = {3294--3301},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse},
  url          = {http://dx.doi.org/10.1182/blood-2010-08-301796},
  volume       = {117},
  year         = {2011},
}