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First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation

The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of i...

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Autores principales: Piccaluga, Pier Paolo, Paolini, Stefania, Bertuzzi, Clara, De Leo, Antonio, Rosti, Gianantonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514971/
https://www.ncbi.nlm.nih.gov/pubmed/23226701
http://dx.doi.org/10.2147/JBM.S13067
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author Piccaluga, Pier Paolo
Paolini, Stefania
Bertuzzi, Clara
De Leo, Antonio
Rosti, Gianantonio
author_facet Piccaluga, Pier Paolo
Paolini, Stefania
Bertuzzi, Clara
De Leo, Antonio
Rosti, Gianantonio
author_sort Piccaluga, Pier Paolo
collection PubMed
description The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients.
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spelling pubmed-35149712012-12-06 First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation Piccaluga, Pier Paolo Paolini, Stefania Bertuzzi, Clara De Leo, Antonio Rosti, Gianantonio J Blood Med Review The therapeutic landscape of chronic myeloid leukemia (CML) has changed dramatically in the last decade. In particular, the availability of imatinib mesylate, a tyrosine kinase inhibitor targeting BCR-ABL, has led to profound and durable remissions in the majority of patients. However, a couple of issues have emerged and partially obscured this scenario. First, it has become clear that a significant proportion of patients either present with primary resistance to imatinib or develop secondary resistance sooner or later during treatment. Second, although the drug is generally well tolerated, a percentage of patients eventually cease treatment because of toxicity. Bearing this in mind, second-generation tyrosine kinase inhibitors have been introduced, including nilotinib. Phase I and II studies indicate remarkable activity for this compound in CML cases resistant to imatinib, including some of those carrying BCR-ABL1 mutants. More recently, two Phase II studies and a III randomized Phase clinical trial demonstrated the superiority of nilotinib compared with imatinib in terms of complete cytogenetic and major molecular responses, which are two relevant surrogate measures of long-term survival in CML. In this paper, we review the most relevant data on nilotinib as first-line treatment for CML, and discuss the rationale for its routine use, as well as some possible future perspectives for CML patients. Dove Medical Press 2012-11-29 /pmc/articles/PMC3514971/ /pubmed/23226701 http://dx.doi.org/10.2147/JBM.S13067 Text en © 2012 Piccaluga et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
spellingShingle Review
Piccaluga, Pier Paolo
Paolini, Stefania
Bertuzzi, Clara
De Leo, Antonio
Rosti, Gianantonio
First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title_full First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title_fullStr First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title_full_unstemmed First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title_short First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
title_sort first-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514971/
https://www.ncbi.nlm.nih.gov/pubmed/23226701
http://dx.doi.org/10.2147/JBM.S13067
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