title: Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study.
abstract: Nilotinib (Tasigna) is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (CML-CP) who are newly diagnosed or intolerant of or resistant to imatinib. The 48-month follow-up data for patients with CML-CP treated with nilotinib after imatinib resistance or intolerance on an international phase II study were analyzed. Overall, 59% of patients achieved major cytogenetic response; 45% achieved complete cytogenetic response while on study. The estimated rate of overall survival (OS) and progression-free survival (PFS) at 48 months was 78% and 57%, respectively. Deeper levels of molecular responses at 3 and 6 months were highly positively correlated with long-term outcomes, including PFS and OS at 48 months. Of the 321 patients initially enrolled in the study, 98 (31%) were treated for at least 48 months. Discontinuations were primarily due to disease progression (30%) or adverse events (21%). Nilotinib is safe and effective for long-term use in responding patients with CML-CP who are intolerant of or resistant to imatinib. Further significant improvements in therapy are required for patients who are resistant or intolerant to imatinib.
authors: HRB Clinical Research Facilities, National University of Ireland Galway and Trinity College, Dublin, Ireland. frankgiles@aol.com
authors: F J
authors: FJ
authors: Giles
authors: P D
authors: PD
authors: le Coutre
authors: J
authors: J
authors: Pinilla-Ibarz
authors: R A
authors: RA
authors: Larson
authors: N
authors: N
authors: Gattermann
authors: O G
authors: OG
authors: Ottmann
authors: A
authors: A
authors: Hochhaus
authors: J P
authors: JP
authors: Radich
authors: G
authors: G
authors: Saglio
authors: T P
authors: TP
authors: Hughes
authors: G
authors: G
authors: Martinelli
authors: D-W
authors: DW
authors: Kim
authors: S
authors: S
authors: Novick
authors: K
authors: K
authors: Gillis
authors: X
authors: X
authors: Fan
authors: J
authors: J
authors: Cortes
authors: M
authors: M
authors: Baccarani
authors: H M
authors: HM
authors: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D007390:International Agencies; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib