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A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome
The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with poor prognosis. We hypothesized that quizartinib, a selective and potent FLT3 inhibitor, with azacitidine (AZA) or low-dose cytarabine (LDAC) might improve the outcomes i...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Fondazione Ferrata Storti
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327731/ https://www.ncbi.nlm.nih.gov/pubmed/33853292 http://dx.doi.org/10.3324/haematol.2020.263392 |
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author | Swaminathan, Mahesh Kantarjian, Hagop M. Levis, Mark Guerra, Veronica Borthakur, Gautam Alvarado, Yesid DiNardo, Courtney D. Kadia, Tapan Garcia-Manero, Guillermo Ohanian, Maro Daver, Naval Konopleva, Marina Pemmaraju, Naveen Ferrajol, Alessandra Andreeff, Michael Jain, Nitin Estrov, Zeev Jabbour, Elias J. Wierda, William G. Pierce, Sherry Pinsoy, Maria Rhona Xiao, Lianchun Ravandi, Farhad Cortes, Jorge E. |
author_facet | Swaminathan, Mahesh Kantarjian, Hagop M. Levis, Mark Guerra, Veronica Borthakur, Gautam Alvarado, Yesid DiNardo, Courtney D. Kadia, Tapan Garcia-Manero, Guillermo Ohanian, Maro Daver, Naval Konopleva, Marina Pemmaraju, Naveen Ferrajol, Alessandra Andreeff, Michael Jain, Nitin Estrov, Zeev Jabbour, Elias J. Wierda, William G. Pierce, Sherry Pinsoy, Maria Rhona Xiao, Lianchun Ravandi, Farhad Cortes, Jorge E. |
author_sort | Swaminathan, Mahesh |
collection | PubMed |
description | The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with poor prognosis. We hypothesized that quizartinib, a selective and potent FLT3 inhibitor, with azacitidine (AZA) or low-dose cytarabine (LDAC) might improve the outcomes in patients with FLT3-ITD-mutated AML. In this open-label phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD AML or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus AZA or LDAC. Seventy-three patients were treated (34 frontline, 39 first salvage). With regard to previously untreated patients, the composite response (CRc) rate was 87% (n=13/15: 8 complete responses [CR], 4 CR with incomplete hematologic recovery [CRi], 1 CR without platelet recovery [CRp]) among the patients treated with quizartinib/AZA and 74% (n=14/19: 1 CR, 8 CRi, 5 CRp) among those treated with quizartinib/LDAC. The median overall survival was 19.2 months for the cohort treated with quizartinib/AZA cohort and 8.5 months for the patients treated with quizartinib/LDAC; the corresponding relapse-free survival figures were 10.5 and 6.4 months, respectively. With regard to previously treated patients, the CRc rate was 64% (n=16/25 in the quizartinib/AZA cohort and 29% (n=4/14)) in the quizartinib/LDAC cohort. The median overall survival for patients treated with quizartinib/AZA and quizartinib/LDAC was 12.8 versus 4 months, respectively. QTc prolongation grade 3 occurred in only one patient in each cohort. Quizartinib-based combinations, particularly with AZA, appear effective in both frontline and first salvage therapy for patients with FLT3-ITD-mutated AML and are well tolerated. ClinicalTrials.gov identifier: NCT01892371. |
format | Online Article Text |
id | pubmed-8327731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Fondazione Ferrata Storti |
record_format | MEDLINE/PubMed |
spelling | pubmed-83277312021-08-11 A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome Swaminathan, Mahesh Kantarjian, Hagop M. Levis, Mark Guerra, Veronica Borthakur, Gautam Alvarado, Yesid DiNardo, Courtney D. Kadia, Tapan Garcia-Manero, Guillermo Ohanian, Maro Daver, Naval Konopleva, Marina Pemmaraju, Naveen Ferrajol, Alessandra Andreeff, Michael Jain, Nitin Estrov, Zeev Jabbour, Elias J. Wierda, William G. Pierce, Sherry Pinsoy, Maria Rhona Xiao, Lianchun Ravandi, Farhad Cortes, Jorge E. Haematologica Article The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation in acute myeloid leukemia (AML) is associated with poor prognosis. We hypothesized that quizartinib, a selective and potent FLT3 inhibitor, with azacitidine (AZA) or low-dose cytarabine (LDAC) might improve the outcomes in patients with FLT3-ITD-mutated AML. In this open-label phase I/II trial, patients of any age receiving first-salvage treatment for FLT3-ITD AML or age >60 years with untreated myelodysplastic syndrome or AML were treated with quizartinib plus AZA or LDAC. Seventy-three patients were treated (34 frontline, 39 first salvage). With regard to previously untreated patients, the composite response (CRc) rate was 87% (n=13/15: 8 complete responses [CR], 4 CR with incomplete hematologic recovery [CRi], 1 CR without platelet recovery [CRp]) among the patients treated with quizartinib/AZA and 74% (n=14/19: 1 CR, 8 CRi, 5 CRp) among those treated with quizartinib/LDAC. The median overall survival was 19.2 months for the cohort treated with quizartinib/AZA cohort and 8.5 months for the patients treated with quizartinib/LDAC; the corresponding relapse-free survival figures were 10.5 and 6.4 months, respectively. With regard to previously treated patients, the CRc rate was 64% (n=16/25 in the quizartinib/AZA cohort and 29% (n=4/14)) in the quizartinib/LDAC cohort. The median overall survival for patients treated with quizartinib/AZA and quizartinib/LDAC was 12.8 versus 4 months, respectively. QTc prolongation grade 3 occurred in only one patient in each cohort. Quizartinib-based combinations, particularly with AZA, appear effective in both frontline and first salvage therapy for patients with FLT3-ITD-mutated AML and are well tolerated. ClinicalTrials.gov identifier: NCT01892371. Fondazione Ferrata Storti 2021-04-15 /pmc/articles/PMC8327731/ /pubmed/33853292 http://dx.doi.org/10.3324/haematol.2020.263392 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. |
spellingShingle | Article Swaminathan, Mahesh Kantarjian, Hagop M. Levis, Mark Guerra, Veronica Borthakur, Gautam Alvarado, Yesid DiNardo, Courtney D. Kadia, Tapan Garcia-Manero, Guillermo Ohanian, Maro Daver, Naval Konopleva, Marina Pemmaraju, Naveen Ferrajol, Alessandra Andreeff, Michael Jain, Nitin Estrov, Zeev Jabbour, Elias J. Wierda, William G. Pierce, Sherry Pinsoy, Maria Rhona Xiao, Lianchun Ravandi, Farhad Cortes, Jorge E. A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title | A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title_full | A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title_fullStr | A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title_full_unstemmed | A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title_short | A phase I/II study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
title_sort | phase i/ii study of the combination of quizartinib with azacitidine or low-dose cytarabine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327731/ https://www.ncbi.nlm.nih.gov/pubmed/33853292 http://dx.doi.org/10.3324/haematol.2020.263392 |
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