title: Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment.
abstract: Imatinib mesylate, a targeted inhibitor of BCR-ABL tyrosine kinase, is the standard of care for chronic myeloid leukemia (CML). A phase 2 trial of imatinib in late chronic-phase (CP) CML after interferon-alpha (IFNalpha) failure enrolled 532 patients, 454 with a confirmed diagnosis of CP CML. Median time from diagnosis was 34 months; median duration of imatinib treatment was 65 months. Cumulative best rates of major cytogenetic response (MCyR) and complete cytogenetic response (CCyR) were 67% and 57%, respectively. At the 5-year landmark, 184 (41%) of the 454 patients are in CCyR. At more than 6 years, 199 (44%) of the 454 patients remain on imatinib. Most responses occurred within 12 months of starting imatinib; however, some patients achieved initial MCyR and CCyR more than 5 years after imatinib initiation. Estimated rates of freedom from progression to accelerated phase (AP) and blastic phase (BP) and overall survival at 6 years were 61% and 76%, respectively. Both freedom from progression to AP/BP and overall survival (OS) were associated with cytogenetic response level at 12 months. No increase in rates of serious adverse events was observed with continuous use of imatinib for up to 6.5 years, compared with earlier time points. Imatinib continues to be an effective and safe therapy for patients with CP CML after failure of IFN.
authors.affiliation: Medizinische Fakultaet Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hochhaus
authors.forename: Brian
authors.initials: B
authors.lastname: Druker
authors.forename: Charles
authors.initials: C
authors.lastname: Sawyers
authors.forename: Francois
authors.initials: F
authors.lastname: Guilhot
authors.forename: Charles A
authors.initials: CA
authors.lastname: Schiffer
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
authors.forename: Dietger W
authors.initials: DW
authors.lastname: Niederwieser
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti-Passerini
authors.forename: Carlo
authors.initials: C
authors.lastname: Gambacorti
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.forename: John
authors.initials: J
authors.lastname: Goldman
authors.forename: Thomas
authors.initials: T
authors.lastname: Fischer
authors.forename: Stephen G
authors.initials: SG
authors.lastname: O'Brien
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Reiffers
authors.forename: Manisha
authors.initials: M
authors.lastname: Mone
authors.forename: Tillmann
authors.initials: T
authors.lastname: Krahnke
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D018450:Disease Progression; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000627:therapeutic use*; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000473:pathology*; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use*; D011743:Pyrimidines / Q000009:adverse effects* / Q000627:therapeutic use*; D016879:Salvage Therapy; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate