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Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study
BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism all...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elmer Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430861/ https://www.ncbi.nlm.nih.gov/pubmed/32855753 http://dx.doi.org/10.14740/jh676 |
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author | Alexander, William Davis, Sarah Ramakrishna, Raj Manoharan, Arumugam |
author_facet | Alexander, William Davis, Sarah Ramakrishna, Raj Manoharan, Arumugam |
author_sort | Alexander, William |
collection | PubMed |
description | BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism allows adequate target blockade at much lower doses due to prolonged effect. Dose reductions or interruptions are often used in clinical practice to limit its distinct side effects, including diarrhea, bleeding and atrial fibrillation and emerging evidence exists that these do not hinder efficacy. Using a retrospective clinical audit of a single-center outpatient hematology clinic, we aimed to examine outcomes and toxicities of a reduced frequency dose regimen of ibrutinib in patients beyond the confines of a clinical trial. METHODS: A small pilot study was conducted on 16 voluntary CLL patients that had achieved partial or complete remission on standard dose ibrutinib and were considering cessation due to side effects. Patients were consented and prescribed a 420 mg thrice weekly regimen and side effects and outcomes were recorded on routine review. A retrospective clinical audit from 2015 to 2018 was then conducted to compare pilot participants to patients that had remained on standard dosing and results from the extended follow-up of the landmark RESONATE trial. RESULTS: None of the 16 patients in the pilot relapsed or died during the study period equating to a 100% progression free and overall survival. There was resolution or reduction in all side effects reported following switchover; however, the study was too small to establish a statistical relationship. CONCLUSION: This is the first study to demonstrate use of a thrice weekly regimen to reduce ibrutinib-related toxicities whilst preserving safety and efficacy in patients following complete or partial remission on standard dose therapy. Higher powered, prospective studies are required to establish positive health and financial implications in the elderly and vulnerable CLL demographic. |
format | Online Article Text |
id | pubmed-7430861 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elmer Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74308612020-09-01 Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study Alexander, William Davis, Sarah Ramakrishna, Raj Manoharan, Arumugam J Hematol Original Article BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism allows adequate target blockade at much lower doses due to prolonged effect. Dose reductions or interruptions are often used in clinical practice to limit its distinct side effects, including diarrhea, bleeding and atrial fibrillation and emerging evidence exists that these do not hinder efficacy. Using a retrospective clinical audit of a single-center outpatient hematology clinic, we aimed to examine outcomes and toxicities of a reduced frequency dose regimen of ibrutinib in patients beyond the confines of a clinical trial. METHODS: A small pilot study was conducted on 16 voluntary CLL patients that had achieved partial or complete remission on standard dose ibrutinib and were considering cessation due to side effects. Patients were consented and prescribed a 420 mg thrice weekly regimen and side effects and outcomes were recorded on routine review. A retrospective clinical audit from 2015 to 2018 was then conducted to compare pilot participants to patients that had remained on standard dosing and results from the extended follow-up of the landmark RESONATE trial. RESULTS: None of the 16 patients in the pilot relapsed or died during the study period equating to a 100% progression free and overall survival. There was resolution or reduction in all side effects reported following switchover; however, the study was too small to establish a statistical relationship. CONCLUSION: This is the first study to demonstrate use of a thrice weekly regimen to reduce ibrutinib-related toxicities whilst preserving safety and efficacy in patients following complete or partial remission on standard dose therapy. Higher powered, prospective studies are required to establish positive health and financial implications in the elderly and vulnerable CLL demographic. Elmer Press 2020-09 2020-08-14 /pmc/articles/PMC7430861/ /pubmed/32855753 http://dx.doi.org/10.14740/jh676 Text en Copyright 2020, Alexander et al. http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Alexander, William Davis, Sarah Ramakrishna, Raj Manoharan, Arumugam Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title | Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title_full | Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title_fullStr | Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title_full_unstemmed | Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title_short | Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study |
title_sort | outcomes of reduced frequency dosing of ibrutinib in chronic lymphocytic leukemia patients following complete or partial remission: a pilot study |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430861/ https://www.ncbi.nlm.nih.gov/pubmed/32855753 http://dx.doi.org/10.14740/jh676 |
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