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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1095870/full |
| _version_ | 1797870439926595584 |
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| author | Sarah Morin Federica Giannotti Anne-Claire Mamez Amandine Pradier Stavroula Masouridi-Levrat Federico Simonetta Federico Simonetta Yves Chalandon Yves Chalandon |
| author_facet | Sarah Morin Federica Giannotti Anne-Claire Mamez Amandine Pradier Stavroula Masouridi-Levrat Federico Simonetta Federico Simonetta Yves Chalandon Yves Chalandon |
| author_sort | Sarah Morin |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-10T00:27:32Z |
| format | Article |
| id | doaj.art-4112719bae8044f9936b6400c0213214 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T00:27:32Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4112719bae8044f9936b6400c02132142023-03-15T05:42:13ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.10958701095870Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruptionSarah Morin0Federica Giannotti1Anne-Claire Mamez2Amandine Pradier3Stavroula Masouridi-Levrat4Federico Simonetta5Federico Simonetta6Yves Chalandon7Yves Chalandon8Division of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandTranslational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandDivision of Hematology, Department of Oncology, Geneva University Hospitals, Geneva, SwitzerlandTranslational Research Center for Oncohematology, Department of Medicine, Faculty of Medicine, University of Geneva, Geneva, SwitzerlandSorafenib 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.https://www.frontiersin.org/articles/10.3389/fonc.2023.1095870/fullsorafenibmaintenanceHSCT = hematopoietic stem cell transplantacute myeloid leukemiadrug toxicity and adverse effect |
| spellingShingle | Sarah Morin Federica Giannotti Anne-Claire Mamez Amandine Pradier Stavroula Masouridi-Levrat Federico Simonetta Federico Simonetta Yves Chalandon Yves Chalandon Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption Frontiers in Oncology sorafenib maintenance HSCT = hematopoietic stem cell transplant acute myeloid leukemia drug toxicity and adverse effect |
| 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 | sorafenib maintenance HSCT = hematopoietic stem cell transplant acute myeloid leukemia drug toxicity and adverse effect |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1095870/full |
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