title: Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha.
abstract: We reviewed 261 patients with chronicphase chronic myelogenous leukemia (CML) after interferon-alpha (IFN-alpha) failure treated with imatinib mesylate 400 mg daily. With a median follow-up time of 45 months, the major cytogenetic response rate was 73% and the complete cytogenetic response rate 63%. The estimated 4-year survival rate was 86%. Multivariate analysis for survival identified hematologic resistance to IFN-alpha (P =.01), splenomegaly (P =.03), and lack of any cytogenetic response after 3 months of therapy (P =.01) to have independent poor prognostic significance. Patients could be divided into good (no adverse factors), intermediate (1 adverse factor), and poor-risk groups (2 or 3 adverse factors; 12% of patients) with estimated 4-year survival rates of 96%, 86%, and 49%, respectively (P <.00001). The 4-year cumulative major molecular response (quantitative reverse transcriptase-polymerase chain reaction [Q-PCR] = BCR-ABL/ABL less than 0.05%) rate was 43% and complete molecular response rate (BCR-ABL undetectable) 26%. Compared with a historical group of 251 similar patients treated with nonimatinib therapies, imatinib mesylate was associated with a better 4-year survival rate (86% versus 43%; P <.0001); the survival advantage was confirmed by multivariate analysis (hazard ratio, 0.19; P <.0001).
authors.affiliation: Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. hkantarj@mdanderson.org
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Cortes
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Deborah
authors.initials: D
authors.lastname: Thomas
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Rios
authors.forename: Jianqin
authors.initials: J
authors.lastname: Shan
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D018450:Disease Progression; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl