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Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study

A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with...

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Autores principales: Bertoli, Sarah, Dumas, Pierre-Yves, Bérard, Emilie, Largeaud, Laetitia, Bidet, Audrey, Delabesse, Eric, Tavitian, Suzanne, Gadaud, Noémie, Leguay, Thibaut, Leroy, Harmony, Rieu, Jean-Baptiste, Vial, Jean-Philippe, Vergez, François, Lechevalier, Nicolas, Luquet, Isabelle, Klein, Emilie, Sarry, Audrey, De Grande, Anne-Charlotte, Récher, Christian, Pigneux, Arnaud
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226007/
https://www.ncbi.nlm.nih.gov/pubmed/32218221
http://dx.doi.org/10.3390/cancers12040773
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author Bertoli, Sarah
Dumas, Pierre-Yves
Bérard, Emilie
Largeaud, Laetitia
Bidet, Audrey
Delabesse, Eric
Tavitian, Suzanne
Gadaud, Noémie
Leguay, Thibaut
Leroy, Harmony
Rieu, Jean-Baptiste
Vial, Jean-Philippe
Vergez, François
Lechevalier, Nicolas
Luquet, Isabelle
Klein, Emilie
Sarry, Audrey
De Grande, Anne-Charlotte
Récher, Christian
Pigneux, Arnaud
author_facet Bertoli, Sarah
Dumas, Pierre-Yves
Bérard, Emilie
Largeaud, Laetitia
Bidet, Audrey
Delabesse, Eric
Tavitian, Suzanne
Gadaud, Noémie
Leguay, Thibaut
Leroy, Harmony
Rieu, Jean-Baptiste
Vial, Jean-Philippe
Vergez, François
Lechevalier, Nicolas
Luquet, Isabelle
Klein, Emilie
Sarry, Audrey
De Grande, Anne-Charlotte
Récher, Christian
Pigneux, Arnaud
author_sort Bertoli, Sarah
collection PubMed
description A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R FLT3-mutated AML included in the Toulouse–Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory (n = 48, 27.6%) or relapsed (n = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy (n = 99, 56.9%), azacitidine or low-dose cytarabine (n = 9, 5.1%), other low-intensity treatments (n = 17, 9.8%), immediate allogeneic stem cell transplantation (n = 4, 2.3%) or best supportive care only (n = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, n = 32, 28.1%; relapsed, n = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% (n = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0–32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27–45), 24.7% (95%CI: 1–33) and 19.7% (95%CI: 1–28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R FLT3-mutated AML remains very poor with standard salvage therapy.
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spelling pubmed-72260072020-05-18 Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study Bertoli, Sarah Dumas, Pierre-Yves Bérard, Emilie Largeaud, Laetitia Bidet, Audrey Delabesse, Eric Tavitian, Suzanne Gadaud, Noémie Leguay, Thibaut Leroy, Harmony Rieu, Jean-Baptiste Vial, Jean-Philippe Vergez, François Lechevalier, Nicolas Luquet, Isabelle Klein, Emilie Sarry, Audrey De Grande, Anne-Charlotte Récher, Christian Pigneux, Arnaud Cancers (Basel) Article A recent phase 3 trial showed that the outcome of patients with relapsed/refractory (R/R) FLT3-mutated acute myeloid leukemia (AML) improved with gilteritinib, a single-agent second-generation FLT3 tyrosine kinase inhibitor (TKI), compared with standard of care. In this trial, the response rate with standard therapy was particularly low. We retrospectively assessed the characteristics and outcome of patients with R/R FLT3-mutated AML included in the Toulouse–Bordeaux DATAML registry. Among 347 patients who received FLT3 TKI-free intensive chemotherapy as first-line treatment, 174 patients were refractory (n = 48, 27.6%) or relapsed (n = 126, 72.4%). Salvage treatments consisted of intensive chemotherapy (n = 99, 56.9%), azacitidine or low-dose cytarabine (n = 9, 5.1%), other low-intensity treatments (n = 17, 9.8%), immediate allogeneic stem cell transplantation (n = 4, 2.3%) or best supportive care only (n = 45, 25.9%). Among the 114 patients who previously received FLT3 TKI-free intensive chemotherapy as first-line treatment (refractory, n = 32, 28.1%; relapsed, n = 82, 71.9%), the rate of CR (complete remission) or CRi (complete remission with incomplete hematologic recovery) after high- or low-intensity salvage treatment was 50.0%, with a bridge to transplant in 34.2% (n = 39) of cases. The median overall survival (OS) was 8.2 months (interquartile range, 3.0–32); 1-, 3- and 5-year OS rates were 36.0% (95%CI: 27–45), 24.7% (95%CI: 1–33) and 19.7% (95%CI: 1–28), respectively. In this real-word study, although response rate appeared higher than the controlled arm of the ADMIRAL trial, the outcome of patients with R/R FLT3-mutated AML remains very poor with standard salvage therapy. MDPI 2020-03-25 /pmc/articles/PMC7226007/ /pubmed/32218221 http://dx.doi.org/10.3390/cancers12040773 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bertoli, Sarah
Dumas, Pierre-Yves
Bérard, Emilie
Largeaud, Laetitia
Bidet, Audrey
Delabesse, Eric
Tavitian, Suzanne
Gadaud, Noémie
Leguay, Thibaut
Leroy, Harmony
Rieu, Jean-Baptiste
Vial, Jean-Philippe
Vergez, François
Lechevalier, Nicolas
Luquet, Isabelle
Klein, Emilie
Sarry, Audrey
De Grande, Anne-Charlotte
Récher, Christian
Pigneux, Arnaud
Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title_full Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title_fullStr Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title_full_unstemmed Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title_short Outcome of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia before Second-Generation FLT3 Tyrosine Kinase Inhibitors: A Toulouse–Bordeaux DATAML Registry Study
title_sort outcome of relapsed or refractory flt3-mutated acute myeloid leukemia before second-generation flt3 tyrosine kinase inhibitors: a toulouse–bordeaux dataml registry study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226007/
https://www.ncbi.nlm.nih.gov/pubmed/32218221
http://dx.doi.org/10.3390/cancers12040773
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