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BMC Cancer. 2013 Apr 2;13:173. doi: 10.1186/1471-2407-13-173.

Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia.

Abstract

BACKGROUND:

We evaluated BCR-ABL1 kinetics in patients treated with nilotinib and analyzed whether a dynamic model of changes in BCR-ABL1 levels over time could be used to predict long-term responses.

METHODS:

Patients from the nilotinib registration trial (CAMN107A2101; registered at http://www.clinicaltrials.gov as NCT00109707) who had imatinib-resistant or -intolerant Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP) or accelerated phase with BCR-ABL1 > 10% (on the international scale [IS]) at baseline and, in the first 6 months, had at least three BCR-ABL1 transcript measurements and an average daily dose of at least 720 mg were included in this analysis (N = 123).

RESULTS:

More than half of patients (65/123; 53%) had a slow monophasic response and the remainder (58/123; 47%) had a biphasic response, in which patients had a rapid initial decrease in BCR-ABL1 transcripts followed by a more gradual response. The biphasic response type strongly correlated with improved event-free survival (EFS). Data in the first 6 months of follow-up were sufficient to predict EFS at 24 months.

CONCLUSIONS:

Unlike newly diagnosed patients with Ph+ CML-CP-in whom the majority had a biphasic response-approximately half of patients with imatinib-resistant or -intolerant CML had a slower, monophasic response. Second-line patients who did have a biphasic response had an EFS outlook similar to that of newly diagnosed patients treated with imatinib. Our model was comparable to using BCR-ABL1 (IS) ≤ 10% at 6 months as a threshold for predicting EFS.

PMID:
23547655
PMCID:
PMC3646679
DOI:
10.1186/1471-2407-13-173
[Indexed for MEDLINE]
Free PMC Article

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