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Type: Journal article
Title: Chronic phase chronic myeloid leukemia patients with low OCT-1 activity randomized to high-dose imatinib achieve better responses and have lower failure rates than those randomized to standard-dose imatinib
Author: White, D.
Radich, J.
Soverini, S.
Saunders, V.
Frede, A.
Dang, P.
Cilloni, D.
Lin, P.
Mongay, L.
Woodman, R.
Manley, P.
Slader, C.
Kim, D.
Pane, F.
Martinelli, G.
Saglio, G.
Hughes, T.
Citation: Haematologica, 2012; 97(6):907-914
Publisher: Ferrata Storti Foundation
Issue Date: 2012
ISSN: 0390-6078
Statement of
Deborah L. White, Jerald Radich, Simona Soverini, Verity A. Saunders, Amity K. Frede, Phuong Dang, Daniela Cilloni, Peter Lin, Lidia Mongay, Richard Woodman, Paul Manley, Cassandra Slader, Dong Wook Kim, Fabrizio Pane, Giovanni Martinelli, Giuseppe Saglio and Timothy P. Hughes
Abstract: BACKGROUND: The functional activity of the organic cation transporter 1 (OCT-1) protein (OCT-1 activity) is an excellent predictor of molecular response and progression-free survival in patients with newly diagnosed chronic phase chronic myeloid leukemia treated with imatinib as front-line therapy. DESIGN AND METHODS: In this study the predictive value of OCT-1 activity in patients treated with imatinib 400 mg/day or 800 mg/day was evaluated in relation to trough imatinib plasma levels assessed in 100 patients enrolled in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) trial. RESULTS: The rate of major molecular responses by 24 months in patients on imatinib 400 mg/day was significantly higher in those with high OCT-1 activity than in those with low OCT-1 activity (low OCT-1 activity, 57% of patients; high OCT-1 activity, 100%; P<0.001); the corresponding difference in patients treated with imatinib 800 mg/day did not reach statistical significance (low OCT-1 activity, 68%; high OCT-1 activity, 95%; P=0.073). In addition, the combination of low trough imatinib levels (<1200 ng/mL) and low OCT-1 activity defined a group of patients who had the lowest rates of major molecular response (47%) by 24 months compared to all other patients (81%, P=0.009). These patients were also at the highest risk of failed imatinib therapy when compared to all other patients (P<0.001). CONCLUSIONS: High-dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. Among patients with high OCT-1 activity, neither higher imatinib dose nor monitoring imatinib trough levels was found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia.
Keywords: Chronic myeloid leukemia; imatinib; OCT-1 activity; imatinib trough levels
Rights: © 2012 Ferrata Storti Foundation. This is an open-access paper.
RMID: 0020120417
DOI: 10.3324/haematol.2011.056457
Appears in Collections:Medicine publications

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