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

Mark Levis, Farhad Ravandi, Eunice S. Wang, Maria R. Baer, Alexander Perl, Steven Coutre, Harry Erba, Robert K. Stuart, Michele Baccarani, Larry Cripe, Martin S. Tallman, Giovanna Meloni, Lucy A. Godley, Amelia A. Langston, Sergio Amadori, Ian D. Lewis, Arnon Nagler, Richard Stone, Karen Yee, Anjali AdvaniDan Douer, W. Wiktor-Jedrzejczak, Gunnar Juliusson, Mark R. Litzow, Stephen Petersdorf, Miguel Sanz, Hagop M. Kantarjian, Takashi Sato, Lothar Tremmel, Debra M. Bensen-Kennedy, Donald Small, B. Douglas Smith

Research output: Contribution to journalArticle

255 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)3294-3301
Number of pages8
JournalBlood
Volume117
Issue number12
DOIs
StatePublished - Mar 24 2011

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Salvaging
Chemotherapy
Protein-Tyrosine Kinases
Recurrence
Drug Therapy
Acute Myeloid Leukemia
Survival
Pharmacokinetics
Platelets
lestaurtinib
Toxicity
Blood Platelets
Plasmas
Safety
Recovery
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Levis, M., Ravandi, F., Wang, E. S., Baer, M. R., Perl, A., Coutre, S., ... Smith, B. D. (2011). Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. Blood, 117(12), 3294-3301. https://doi.org/10.1182/blood-2010-08-301796

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; Cripe, Larry; Tallman, Martin S.; Meloni, Giovanna; Godley, Lucy A.; Langston, Amelia A.; Amadori, Sergio; Lewis, Ian D.; Nagler, Arnon; Stone, Richard; Yee, Karen; Advani, Anjali; Douer, Dan; Wiktor-Jedrzejczak, W.; Juliusson, Gunnar; Litzow, Mark R.; Petersdorf, Stephen; Sanz, Miguel; Kantarjian, Hagop M.; Sato, Takashi; Tremmel, Lothar; Bensen-Kennedy, Debra M.; Small, Donald; Smith, B. Douglas.

In: Blood, Vol. 117, No. 12, 24.03.2011, p. 3294-3301.

Research output: Contribution to journalArticle

Levis, M, Ravandi, F, Wang, ES, Baer, MR, Perl, A, Coutre, S, Erba, H, Stuart, RK, Baccarani, M, Cripe, L, Tallman, MS, Meloni, G, Godley, LA, Langston, AA, Amadori, S, Lewis, ID, Nagler, A, Stone, R, Yee, K, Advani, A, Douer, D, Wiktor-Jedrzejczak, W, Juliusson, G, Litzow, MR, Petersdorf, S, Sanz, M, Kantarjian, HM, Sato, T, Tremmel, L, Bensen-Kennedy, DM, Small, D & Smith, BD 2011, 'Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse', Blood, vol. 117, no. 12, pp. 3294-3301. https://doi.org/10.1182/blood-2010-08-301796
Levis, Mark ; Ravandi, Farhad ; Wang, Eunice S. ; Baer, Maria R. ; Perl, Alexander ; Coutre, Steven ; Erba, Harry ; Stuart, Robert K. ; Baccarani, Michele ; Cripe, Larry ; Tallman, Martin S. ; Meloni, Giovanna ; Godley, Lucy A. ; Langston, Amelia A. ; Amadori, Sergio ; Lewis, Ian D. ; Nagler, Arnon ; Stone, Richard ; Yee, Karen ; Advani, Anjali ; Douer, Dan ; Wiktor-Jedrzejczak, W. ; Juliusson, Gunnar ; Litzow, Mark R. ; Petersdorf, Stephen ; Sanz, Miguel ; Kantarjian, Hagop M. ; Sato, Takashi ; Tremmel, Lothar ; Bensen-Kennedy, Debra M. ; Small, Donald ; Smith, B. Douglas. / Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. In: Blood. 2011 ; Vol. 117, No. 12. pp. 3294-3301.
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AU - Levis, Mark

AU - Ravandi, Farhad

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AU - Baer, Maria R.

AU - Perl, Alexander

AU - Coutre, Steven

AU - Erba, Harry

AU - Stuart, Robert K.

AU - Baccarani, Michele

AU - Cripe, Larry

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

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