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Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse
Open accessAbstract
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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Cited by
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3 -Mutated AML
Perl, A. E., Martinelli, G., Cortes, J. E., Neubauer, A., Berman, E., Paolini, S., Montesinos, P., Baer, M. R., Larson, R. A., Ustun, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1902688 · Cited by 1,287
Self-citationMcMahon, C. M., Ferng, T., Canaani, J., Wang, E. S., Morrissette, J. J. D., Eastburn, D. J., Pellegrino, M., Durruthy-Durruthy, R., Watt, C. D., Asthana, S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1453 · Cited by 446
Self-citationSubtype-specific regulatory network rewiring in acute myeloid leukemia
Assi, S. A., Imperato, M. R., Coleman, D. J. L., Pickin, A., Potluri, S., Ptasinska, A., Chin, P. S., Blair, H., Cauchy, P., James, S. R., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0270-1 · Cited by 179
Outcome of patients with FLT3-mutated acute myeloid leukemia in first relapse
Ravandi, F., Kantarjian, H., Faderl, S., Garcia-Manero, G., O’Brien, S., Koller, C., Pierce, S., Brandt, M., Kennedy, D., Cortes, J., et al. (2010) · Leukemia Research · doi:10.1016/j.leukres.2009.10.001 · Cited by 125
Self-citationChu, S. H., Heiser, D., Li, L., Kaplan, I., Collector, M., Huso, D., Sharkis, S. J., Civin, C., & Small, D. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.027 · Cited by 79
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Metadata
- Authors
- Levis, M., Ravandi, F., Wang, E. S., Baer, M. R., Perl, A., Coutre, S., Erba, H., Stuart, R. K., Baccarani, M., Cripe, L. D., Tallman, M. S., Meloni, G., Godley, L. A., Langston, A. A., Amadori, S., Lewis, I. D., Nagler, A., Stone, R., Yee, K., Advani, A., Douer, D., Wiktor-Jedrzejczak, W., Juliusson, G., Litzow, M. R., Petersdorf, S., Sanz, M., Kantarjian, H. M., Sato, T., Tremmel, L., Bensen-Kennedy, D. M., Small, D., & Smith, B. D.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2011-03-24
- Volume
- 117
- Issue
- 12
- Pages
- 3294-3301
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2016883830
- Cited by
- 398
- References
- 0
- FWCI
- 27.54
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Results from a randomized trial of salvage chemotherapy followed by lestaurtinib for patients with FLT3 mutant AML in first relapse. https://app.cochat.ai/papers/10.1182/blood-2010-08-301796
- The paper
- Levis, M., Ravandi, F., Wang, E. S., Baer, M. R., Perl, A., Coutre, S., Erba, H., Stuart, R. K., Baccarani, M., Cripe, L. D., Tallman, M. S., Meloni, G., Godley, L. A., Langston, A. A., Amadori, S., Lewis, I. D., Nagler, A., Stone, R., Yee, K., . . . 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. https://doi.org/10.1182/blood-2010-08-301796
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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