Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/83386
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Type: Journal article
Title: Rapid initial decline in BCR-ABL1 is associated with superior responses to second-line nilotinib in patients with chronic-phase chronic myeloid leukemia
Author: Stein, A.
Martinelli, G.
Hughes, T.
Muller, M.
Beppu, L.
Gottardi, E.
Branford, S.
Soverini, S.
Woodman, R.
Hochhaus, A.
Kim, D.
Saglio, G.
Radich, J.
Citation: BMC Cancer, 2013; 13(1):1-10
Publisher: BioMed Central Ltd.
Issue Date: 2013
ISSN: 1471-2407
1471-2407
Statement of
Responsibility: 
Andrew M Stein, Giovanni Martinelli, Timothy P Hughes, Martin C Müller, Lan Beppu, Enrico Gottardi, Susan Branford, Simona Soverini, Richard C Woodman, Andreas Hochhaus, Dong-Wook Kim, Giuseppe Saglio and Jerald P Radich
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 webcite 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.
Keywords: Chronic myeloid leukemia; Nilotinib; Mathematical modeling; BCR-ABL; Molecular response
Rights: © 2013 Stein et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
RMID: 0020138081
DOI: 10.1186/1471-2407-13-173
Appears in Collections:Medicine publications

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