Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose

Joanna Waclaw,1 Tomasz Sacha,1 Tomasz Stoklosa,21Department of Hematology, Jagiellonian University Collegium Medicum, Kraków, 2Department of Immunology, Medical University of Warsaw, Warsaw, Poland Abstract: Imatinib was the first tyrosine kinase inhibitor (TKI), successfully used in a c...

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Autores principales:	Waclaw J, Sacha T, Stoklosa T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Diseases of the blood and blood-forming organs RC633-647.5
Acceso en línea:	https://doaj.org/article/9962693a876d47368bf62bed7aa6b1bc
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spelling	oai:doaj.org-article:9962693a876d47368bf62bed7aa6b1bc2021-12-02T04:57:56ZImatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose1179-9889https://doaj.org/article/9962693a876d47368bf62bed7aa6b1bc2015-09-01T00:00:00Zhttps://www.dovepress.com/imatinib-in-the-treatment-of-chronic-myeloid-leukemia-current-perspect-peer-reviewed-article-BLCTThttps://doaj.org/toc/1179-9889Joanna Waclaw,1 Tomasz Sacha,1 Tomasz Stoklosa,21Department of Hematology, Jagiellonian University Collegium Medicum, Kraków, 2Department of Immunology, Medical University of Warsaw, Warsaw, Poland Abstract: Imatinib was the first tyrosine kinase inhibitor (TKI), successfully used in a clinical setting. It inhibits activity of BCR-ABL1 oncogenic tyrosine kinase which is crucial in the pathogenesis of chronic myeloid leukemia (CML). The safety and efficacy of imatinib dose 400 mg daily was established in several clinical studies. Nevertheless, imatinib dose escalation (≥600 mg daily) has been widely explored as an option to improve clinical outcomes. Results of the meta-analysis comparing frontline therapy with imatinib 400 mg daily vs high dose (HD, ≥600 mg daily) in patients with chronic phase CML (CML-CP) showed that the rate of complete cytogenetic response as well as major molecular response (MMR) at 12 months was significantly higher in HD imatinib group. However, HD imatinib does not improve overall survival and progression-free survival. Thus, the routine use of HD imatinib as frontline treatment for CML-CP is not recommended. In patients with CML-CP resistant to standard dose, HD imatinib does not significantly improve patient outcomes without a prior cytogenetic response. Therefore, in second-line therapy, the current CML-CP treatment guidelines do not recommend imatinib dose escalation but the use of second-or third-generation TKIs. In the therapy of TKI-naïve patients with accelerated or blastic phase of CML, HD imatinib (400 mg twice daily) is one of the recommended standards. In case of disease progression while on imatinib, second- or third-generation TKIs should be administered. Keywords: imatinib, standard dose, dose escalation, chronic myeloid leukemia, BCR-ABL1, high doseWaclaw JSacha TStoklosa TDove Medical PressarticleDiseases of the blood and blood-forming organsRC633-647.5ENBlood and Lymphatic Cancer: Targets and Therapy, Vol 2015, Iss default, Pp 101-108 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Diseases of the blood and blood-forming organs RC633-647.5
spellingShingle	Diseases of the blood and blood-forming organs RC633-647.5 Waclaw J Sacha T Stoklosa T Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
description	Joanna Waclaw,1 Tomasz Sacha,1 Tomasz Stoklosa,21Department of Hematology, Jagiellonian University Collegium Medicum, Kraków, 2Department of Immunology, Medical University of Warsaw, Warsaw, Poland Abstract: Imatinib was the first tyrosine kinase inhibitor (TKI), successfully used in a clinical setting. It inhibits activity of BCR-ABL1 oncogenic tyrosine kinase which is crucial in the pathogenesis of chronic myeloid leukemia (CML). The safety and efficacy of imatinib dose 400 mg daily was established in several clinical studies. Nevertheless, imatinib dose escalation (≥600 mg daily) has been widely explored as an option to improve clinical outcomes. Results of the meta-analysis comparing frontline therapy with imatinib 400 mg daily vs high dose (HD, ≥600 mg daily) in patients with chronic phase CML (CML-CP) showed that the rate of complete cytogenetic response as well as major molecular response (MMR) at 12 months was significantly higher in HD imatinib group. However, HD imatinib does not improve overall survival and progression-free survival. Thus, the routine use of HD imatinib as frontline treatment for CML-CP is not recommended. In patients with CML-CP resistant to standard dose, HD imatinib does not significantly improve patient outcomes without a prior cytogenetic response. Therefore, in second-line therapy, the current CML-CP treatment guidelines do not recommend imatinib dose escalation but the use of second-or third-generation TKIs. In the therapy of TKI-naïve patients with accelerated or blastic phase of CML, HD imatinib (400 mg twice daily) is one of the recommended standards. In case of disease progression while on imatinib, second- or third-generation TKIs should be administered. Keywords: imatinib, standard dose, dose escalation, chronic myeloid leukemia, BCR-ABL1, high dose
format	article
author	Waclaw J Sacha T Stoklosa T
author_facet	Waclaw J Sacha T Stoklosa T
author_sort	Waclaw J
title	Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
title_short	Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
title_full	Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
title_fullStr	Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
title_full_unstemmed	Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
title_sort	imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/9962693a876d47368bf62bed7aa6b1bc
work_keys_str_mv	AT waclawj imatinibinthetreatmentofchronicmyeloidleukemiacurrentperspectivesonoptimaldose AT sachat imatinibinthetreatmentofchronicmyeloidleukemiacurrentperspectivesonoptimaldose AT stoklosat imatinibinthetreatmentofchronicmyeloidleukemiacurrentperspectivesonoptimaldose
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Imatinib in the treatment of chronic myeloid leukemia: current perspectives on optimal dose

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