Imatinib produces significantly superior molecular responses compared to interferon alfa plus cytarabine in patients with newly diagnosed chronic myeloid leukemia in chronic phase.
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.
Branford
S
S
Institute of Medical and Veterinary Science, Adelaide, South Australia.
Rudzki
Z
Z
Harper
A
A
Grigg
A
A
Taylor
K
K
Durrant
S
S
Arthur
C
C
Browett
P
P
Schwarer
A P
AP
Ma
D
D
Seymour
J F
JF
Bradstock
K
K
Joske
D
D
Lynch
K
K
Gathmann
I
I
Hughes
T P
TP
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
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