title: First-line treatment of chronic myeloid leukemia with nilotinib: critical evaluation.
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.
authors.affiliation: Hematopathology and Hematology Sections, Department of Hematology and Oncological Sciences, "L and A Seràgnoli", S Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolini
authors.forename: Clara
authors.initials: C
authors.lastname: Bertuzzi
authors.forename: Antonio
authors.initials: A
authors.lastname: De Leo
authors.forename: Gianantonio
authors.initials: G
authors.lastname: Rosti