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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7226007 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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