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Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption

Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patient...

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Autores principales: Morin, Sarah, Giannotti, Federica, Mamez, Anne-Claire, Pradier, Amandine, Masouridi-Levrat, Stavroula, Simonetta, Federico, Chalandon, Yves
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050716/
https://www.ncbi.nlm.nih.gov/pubmed/37007116
http://dx.doi.org/10.3389/fonc.2023.1095870
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author Morin, Sarah
Giannotti, Federica
Mamez, Anne-Claire
Pradier, Amandine
Masouridi-Levrat, Stavroula
Simonetta, Federico
Chalandon, Yves
author_facet Morin, Sarah
Giannotti, Federica
Mamez, Anne-Claire
Pradier, Amandine
Masouridi-Levrat, Stavroula
Simonetta, Federico
Chalandon, Yves
author_sort Morin, Sarah
collection PubMed
description Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption. We conducted a single-center retrospective study on 30 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2017 and 2020 and who received sorafenib maintenance. 26 patients (87%) experienced toxicities leading to dose reduction (n=9) or direct interruption (n=17). Average time on sorafenib was 125 days (range 1-765). Most common toxicities were skin, gastrointestinal, and hematologic. Among patients who had a dose reduction, 4 eventually interrupted the drug and 5 were able to continue. Among patients who interrupted sorafenib because of toxicities, 7 were re-challenged with good tolerance in 3 cases. Overall, 18 patients (60% of the entire cohort) definitively discontinued sorafenib because of toxicities. 14 patients were thereafter switched to midostaurin. Importantly, with a median follow-up of 12 months, the median overall survival was not reached suggesting a positive impact of sorafenib maintenance despite the high rates of treatment interruption. In conclusion, our real-world analysis reveals high rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT. Interestingly, our results suggest the feasibility of re-challenging with sorafenib and/or of switching to other maintenance approaches in case of intolerance.
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spelling pubmed-100507162023-03-30 Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption Morin, Sarah Giannotti, Federica Mamez, Anne-Claire Pradier, Amandine Masouridi-Levrat, Stavroula Simonetta, Federico Chalandon, Yves Front Oncol Oncology Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption. We conducted a single-center retrospective study on 30 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2017 and 2020 and who received sorafenib maintenance. 26 patients (87%) experienced toxicities leading to dose reduction (n=9) or direct interruption (n=17). Average time on sorafenib was 125 days (range 1-765). Most common toxicities were skin, gastrointestinal, and hematologic. Among patients who had a dose reduction, 4 eventually interrupted the drug and 5 were able to continue. Among patients who interrupted sorafenib because of toxicities, 7 were re-challenged with good tolerance in 3 cases. Overall, 18 patients (60% of the entire cohort) definitively discontinued sorafenib because of toxicities. 14 patients were thereafter switched to midostaurin. Importantly, with a median follow-up of 12 months, the median overall survival was not reached suggesting a positive impact of sorafenib maintenance despite the high rates of treatment interruption. In conclusion, our real-world analysis reveals high rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT. Interestingly, our results suggest the feasibility of re-challenging with sorafenib and/or of switching to other maintenance approaches in case of intolerance. Frontiers Media S.A. 2023-03-15 /pmc/articles/PMC10050716/ /pubmed/37007116 http://dx.doi.org/10.3389/fonc.2023.1095870 Text en Copyright © 2023 Morin, Giannotti, Mamez, Pradier, Masouridi-Levrat, Simonetta and Chalandon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Morin, Sarah
Giannotti, Federica
Mamez, Anne-Claire
Pradier, Amandine
Masouridi-Levrat, Stavroula
Simonetta, Federico
Chalandon, Yves
Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title_full Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title_fullStr Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title_full_unstemmed Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title_short Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
title_sort real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for flt3-itd aml reveals high rates of toxicity-related treatment interruption
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050716/
https://www.ncbi.nlm.nih.gov/pubmed/37007116
http://dx.doi.org/10.3389/fonc.2023.1095870
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