title: Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results.
abstract: Nilotinib (Tasigna) is a potent and selective BCR-ABL inhibitor approved for use in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CML-CP) and in patients with CML-CP and accelerated phase (CML-AP) who are resistant to or intolerant of imatinib. Patients with CML-AP (N = 137) with at least 24 months of follow-up or who discontinued early were evaluated to determine the efficacy and tolerability of nilotinib. The majority (55%) of patients achieved a confirmed hematologic response, and 31% attained a confirmed complete hematologic response on nilotinib treatment. Overall, 32% of patients achieved major cytogenetic responses (MCyR), with most being complete cytogenetic responses. Responses were durable, with 66% of patients maintaining MCyR at 24 months. The estimated overall and progression-free survival rates at 24 months were 70% and 33%, respectively. Grade 3/4 neutropenia and thrombocytopenia were each observed in 42% of patients. Non-hematologic adverse events were mostly mild to moderate; the safety profile of nilotinib has not changed with longer follow-up. In all, 20 (15%) patients remained on study at data cutoff. In summary, nilotinib has a manageable safety profile, and can provide favorable long-term outcomes in the pretreated CML-AP patient population for whom treatment options are limited.
authors.affiliation: Charité - University of Medicine Berlin, Berlin, Germany. philipp.lecoutre@charite.de
authors.forename: P D
authors.initials: PD
authors.lastname: le Coutre
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: R
authors.initials: R
authors.lastname: Blakesley
authors.forename: Y
authors.initials: Y
authors.lastname: Shou
authors.forename: N J
authors.initials: NJ
authors.lastname: Gallagher
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D015465:Leukemia, Myeloid, Accelerated Phase / Q000188:drug therapy* / Q000473:pathology; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib