title: Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
abstract: We analyzed molecular responses in 55 newly diagnosed chronic-phase chronic myeloid leukemia (CML) patients enrolled in a phase 3 study (the IRIS trial) comparing imatinib to interferon-alfa plus cytarabine (IFN+AraC). BCR-ABL/BCR% levels were measured by real-time quantitative RT-PCR and were significantly lower for the imatinib-treated patients at all time points up to 18 months, P<0.0001. The median levels for imatinib-treated patients continued to decrease and had not reached a plateau by 24 months. A total of 24 IFN+AraC-treated patients crossed over to imatinib. Once imatinib commenced, the median BCR-ABL/BCR% levels in these patients were not significantly different to those on first-line imatinib for the equivalent number of months. The incidence of progression in imatinib-treated patients, defined by hematologic, cytogenetic or quantitative PCR criteria, was significantly higher in the patients who failed to achieve a 1 log reduction by 3 months or a 2 log reduction by 6 months, P=0.002. A total of 49 patients were screened for BCR-ABL kinase domain mutations. Mutations were detected in two imatinib-treated patients who crossed over from IFN+AraC and both lost their imatinib response. In conclusion, first-line imatinib-treated patients had profound reductions in BCR-ABL/BCR%, which significantly exceeded those of IFN+AraC-treated patients and early measurements were predictive of subsequent response.
authors.affiliation: Institute of Medical and Veterinary Science, Adelaide, South Australia.
authors.forename: S
authors.initials: S
authors.lastname: Branford
authors.forename: Z
authors.initials: Z
authors.lastname: Rudzki
authors.forename: A
authors.initials: A
authors.lastname: Harper
authors.forename: A
authors.initials: A
authors.lastname: Grigg
authors.forename: K
authors.initials: K
authors.lastname: Taylor
authors.forename: S
authors.initials: S
authors.lastname: Durrant
authors.forename: C
authors.initials: C
authors.lastname: Arthur
authors.forename: P
authors.initials: P
authors.lastname: Browett
authors.forename: A P
authors.initials: AP
authors.lastname: Schwarer
authors.forename: D
authors.initials: D
authors.lastname: Ma
authors.forename: J F
authors.initials: JF
authors.lastname: Seymour
authors.forename: K
authors.initials: K
authors.lastname: Bradstock
authors.forename: D
authors.initials: D
authors.lastname: Joske
authors.forename: K
authors.initials: K
authors.lastname: Lynch
authors.forename: I
authors.initials: I
authors.lastname: Gathmann
authors.forename: T P
authors.initials: TP
authors.lastname: Hughes
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D001853:Bone Marrow / Q000378:metabolism; D018592:Cross-Over Studies; D003561:Cytarabine / Q000008:administration & dosage*; D003582:Cytogenetics; D004252:DNA Mutational Analysis; D016044:Fusion Proteins, bcr-abl / Q000097:blood / Q000737:chemistry / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage*; D011379:Prognosis; D017434:Protein Structure, Tertiary; D011743:Pyrimidines / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D010770:Phosphotransferases; D016044:Fusion Proteins, bcr-abl