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

DOI: http://dx.doi.org/10.2147/JBM.S13067

Keywords: chronic myeloid leukemia, nilotinib, targeted therapy, BCR-ABL1

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Abstract:

st-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation Review (1234) Total Article Views Authors: Piccaluga PP, Paolini S, Bertuzzi C, De Leo A, Rosti G Published Date November 2012 Volume 2012:3 Pages 151 - 156 DOI: http://dx.doi.org/10.2147/JBM.S13067 Received: 04 May 2012 Accepted: 12 July 2012 Published: 29 November 2012 Pier Paolo Piccaluga,* Stefania Paolini,* Clara Bertuzzi, Antonio De Leo, Gianantonio Rosti Hematopathology and Hematology Sections, Department of Hematology and Oncological Sciences, "L and A Seràgnoli", S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy *These authors contributed equally to this work Abstract: 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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