title: Prediction of outcomes in patients with Ph+ chronic myeloid leukemia in chronic phase treated with nilotinib after imatinib resistance/intolerance.
abstract: The purpose was to assess predictive factors for outcome in patients with chronic myeloid leukemia (CML) in chronic phase (CML-CP) treated with nilotinib after imatinib failure. Imatinib-resistant and -intolerant patients with CML-CP (n=321) were treated with nilotinib 400 mg twice daily. Of 19 baseline patient and disease characteristics and two response end points analyzed, 10 independent prognostic factors were associated with progression-free survival (PFS). In the multivariate analysis, major cytogenetic response (MCyR) within 12 months, baseline hemoglobin ≥ 120 g/l, baseline basophils <4%, and absence of baseline mutations with low sensitivity to nilotinib were associated with PFS. A prognostic score was created to stratify patients into five groups (best group: 0 of 3 unfavorable risk factors and MCyR by 12 months; worst group: 3 of 3 unfavorable risk factors and no MCyR by 12 months). Estimated 24-month PFS rates were 90%, 79%, 67% and 37% for patients with prognostic scores of 0, 1, 2 and 3, respectively, (no patients with score of 4). Even in the presence of poor disease characteristics, nilotinib provided significant clinical benefit in patients with imatinib-resistant or -intolerant CML. This system may yield insight on the prognosis of patients.
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA. ejabbour@mdanderson.org
authors.forename: E
authors.initials: E
authors.lastname: Jabbour
authors.forename: P D
authors.initials: PD
authors.lastname: le Coutre
authors.forename: J
authors.initials: J
authors.lastname: Cortes
authors.forename: F
authors.initials: F
authors.lastname: Giles
authors.forename: K N
authors.initials: KN
authors.lastname: Bhalla
authors.forename: J
authors.initials: J
authors.lastname: Pinilla-Ibarz
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: N
authors.initials: N
authors.lastname: Gattermann
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
authors.forename: G
authors.initials: G
authors.lastname: Saglio
authors.forename: J P
authors.initials: JP
authors.lastname: Radich
authors.forename: D-W
authors.initials: DW
authors.lastname: Kim
authors.forename: G
authors.initials: G
authors.lastname: Martinelli
authors.forename: J
authors.initials: J
authors.lastname: Reynolds
authors.forename: R C
authors.initials: RC
authors.lastname: Woodman
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib