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A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia
Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractor...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484687/ https://www.ncbi.nlm.nih.gov/pubmed/26150724 http://dx.doi.org/10.2147/TCRM.S73559 |
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author | Tucker, David L Rule, Simon A |
author_facet | Tucker, David L Rule, Simon A |
author_sort | Tucker, David L |
collection | PubMed |
description | Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. |
format | Online Article Text |
id | pubmed-4484687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44846872015-07-06 A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia Tucker, David L Rule, Simon A Ther Clin Risk Manag Review Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Dove Medical Press 2015-06-23 /pmc/articles/PMC4484687/ /pubmed/26150724 http://dx.doi.org/10.2147/TCRM.S73559 Text en © 2015 Tucker and Rule. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Review Tucker, David L Rule, Simon A A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title | A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title_full | A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title_fullStr | A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title_full_unstemmed | A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title_short | A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
title_sort | critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4484687/ https://www.ncbi.nlm.nih.gov/pubmed/26150724 http://dx.doi.org/10.2147/TCRM.S73559 |
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