title: Nilotinib is effective in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blastic phase.
abstract: Nilotinib is a selective inhibitor of BCR-ABL approved for use in newly diagnosed and imatinib-resistant or -intolerant patients with chronic myeloid leukemia (CML) in chronic phase. In this study, 400 mg of nilotinib was administered twice daily to the patients with myeloid (MBP, n=105) or lymphoid blastic phase (LBP, n=31) CML. After a minimum follow-up of 24 months, major hematologic responses were observed in 60% (MBP) and 59% (LBP) of patients. Major cytogenetic responses (MCyR) were attained in 38% (MBP) and 52% (LBP) of patients; and complete cytogenetic responses in 30% and 32%, respectively. Median duration of MCyR was 10.8 (MBP) and 3.2 months (LBP). Median overall survival was 10.1 (MBP) and 7.9 (LBP) months with 12- and 24-month survival of 42% (MBP 44%, LBP 35%) and 27% (MBP 32%, LBP 10%), respectively. Twelve MBP patients and two LBP patients received subsequent stem cell transplantation. Myelosuppression was frequent, with grade 3/4 neutropenia, thrombocytopenia, and anemia in 68%, 63% and 47% of patients, respectively. Grade 3/4 hypophosphatemia, hyperbilirubinemia and lipase elevation were observed in 15%, 11% and 11% of patients, respectively. Nilotinib has significant efficacy in patients with BP CML, but given the limited long-term survival of these patients, novel agents are needed.
authors.affiliation: HRB Clinical Research Facility, National University of Ireland Galway & Trinity College Dublin,, University Road, Galway, Ireland. frankgiles@aol.com
authors.forename: F J
authors.initials: FJ
authors.lastname: Giles
authors.forename: H M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: P D
authors.initials: PD
authors.lastname: le Coutre
authors.forename: M
authors.initials: M
authors.lastname: Baccarani
authors.forename: F-X
authors.initials: FX
authors.lastname: Mahon
authors.forename: R E
authors.initials: RE
authors.lastname: Blakesley
authors.forename: N J
authors.initials: NJ
authors.lastname: Gallagher
authors.forename: K
authors.initials: K
authors.lastname: Gillis
authors.forename: S L
authors.initials: SL
authors.lastname: Goldberg
authors.forename: R A
authors.initials: RA
authors.lastname: Larson
authors.forename: A
authors.initials: A
authors.lastname: Hochhaus
authors.forename: O G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D001752:Blast Crisis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; C498826:nilotinib