TY - JOUR
T1 - Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias
AU - Cortes, Jorge E.
AU - Gambacorti-Passerini, Carlo
AU - Kim, Dong Wook
AU - Kantarjian, Hagop M.
AU - Lipton, Jeff H.
AU - Lahoti, Amit
AU - Talpaz, Moshe
AU - Matczak, Ewa
AU - Barry, Elly
AU - Leip, Eric
AU - Brümmendorf, Tim H.
AU - Khoury, H. Jean
N1 - Funding Information:
Dr Cortes has received research support from Ariad, Bristol-Myers Squibb, Novartis, Pfizer, and Teva, and is a consultant for Ariad, Bristol-Myers Squibb, Novartis, and Pfizer. Dr Gambacorti-Passerini has received research funding from Pfizer and has served as an advisor for Pfizer and Bristol-Myers Squibb. Dr Kim has received research funding from Ariad, Bristol-Myers Squibb, Novartis, and Pfizer; has served as a consultant/advisor for Bristol-Myers Squibb, Novartis, and Pfizer; and has participated on the speakers bureau for and received honoraria from Bristol-Myers Squibb and Novartis. Dr Kantarjian has received research funding from Pfizer. Dr Khoury has received research funding from and attended compensated advisory boards for Bristol-Myers Squibb, Novartis, Teva, Pfizer, and Ariad. Dr Lipton has received research funding and consultant or other fees from Bristol-Myers Squibb, Novartis, Teva, Pfizer, and Ariad, and lecture fees from Bristol-Myers Squibb and Novartis. Dr Talpaz has received research support from Ariad, Novartis, Bristol-Myers Squibb, and Pfizer. Dr Brümmendorf has participated in advisory boards and satellite symposia for Ariad, Bristol-Myers Squibb, Novartis, and Pfizer; has received research funding from Novartis and Pfizer; and holds a patent on the combination of imatinib with hypusination inhibitors. Drs Barry and Leip are employees of Pfizer. Dr Matczak was an employee of Pfizer when the report was initiated. Dr Lahoti has stated no conflicts of interest.
Funding Information:
The studies included in this analysis were sponsored by Pfizer Inc. Employees of Pfizer were involved in study design and in the collection, analysis, and interpretation of data. All authors, including employees of Pfizer, had access to the study data, were involved in the writing of the report, and in the decision to submit the article for publication. Medical writing support was provided by Johna Van Stelten, PhD, and Simon J. Slater, PhD, of Complete Healthcare Communications, LLC, and was funded by Pfizer.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10
Y1 - 2017/10
N2 - We evaluated the incidence of renal adverse events and estimated glomerular filtration rate in patients with Philadelphia chromosome-positive leukemias receiving first-line bosutinib (n = 248) or imatinib (n = 251), or second-line or later bosutinib (n = 570). Results show that long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to those observed with long-term imatinib. Background The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. Patients and Methods Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. Results Time from the last patient's first dose to data cutoff was ≥ 48 months. Renal AEs were reported in 73/570 patients (13%) receiving second-line or later bosutinib, and in 22/248 (9%) and 16/251 (6%) receiving first-line bosutinib and imatinib, respectively. eGFR in patients receiving bosutinib declined over time with more patients developing Grade ≥ 3b eGFR (< 45 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease method) with second-line or later bosutinib (139/570, 24%) compared with first-line bosutinib (26/248, 10%) and imatinib (25/251, 10%); time to Grade ≥ 3b eGFR was shortest with second-line or later bosutinib. Similar proportions of patients receiving second-line or later bosutinib (74/139, 53%), first-line bosutinib (15/26, 58%), and first-line imatinib (15/25, 60%) improved to ≥ 45 mL/min/1.73 m2 eGFR as of the last follow-up. In a regression analysis, first-line treatment with bosutinib versus imatinib was not a significant predictor of Grade ≥ 3b eGFR. Conclusion Long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long-term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely.
AB - We evaluated the incidence of renal adverse events and estimated glomerular filtration rate in patients with Philadelphia chromosome-positive leukemias receiving first-line bosutinib (n = 248) or imatinib (n = 251), or second-line or later bosutinib (n = 570). Results show that long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to those observed with long-term imatinib. Background The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib. Patients and Methods Patients received first-line bosutinib (n = 248) or imatinib (n = 251; phase III trial), or second-line or later bosutinib (phase I/II trial; n = 570). Adverse events (AEs) and changes from baseline in estimated glomerular filtration rate (eGFR) and serum creatinine were assessed. Results Time from the last patient's first dose to data cutoff was ≥ 48 months. Renal AEs were reported in 73/570 patients (13%) receiving second-line or later bosutinib, and in 22/248 (9%) and 16/251 (6%) receiving first-line bosutinib and imatinib, respectively. eGFR in patients receiving bosutinib declined over time with more patients developing Grade ≥ 3b eGFR (< 45 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease method) with second-line or later bosutinib (139/570, 24%) compared with first-line bosutinib (26/248, 10%) and imatinib (25/251, 10%); time to Grade ≥ 3b eGFR was shortest with second-line or later bosutinib. Similar proportions of patients receiving second-line or later bosutinib (74/139, 53%), first-line bosutinib (15/26, 58%), and first-line imatinib (15/25, 60%) improved to ≥ 45 mL/min/1.73 m2 eGFR as of the last follow-up. In a regression analysis, first-line treatment with bosutinib versus imatinib was not a significant predictor of Grade ≥ 3b eGFR. Conclusion Long-term bosutinib treatment is associated with an apparently reversible decline in renal function with frequency and characteristics similar to renal decline observed with long-term imatinib treatment. Patients with risk factors for Grade ≥ 3b eGFR should be monitored closely.
KW - Adverse events
KW - Chronic myeloid leukemia
KW - Renal toxicity
KW - Tyrosine kinase inhibitors
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U2 - 10.1016/j.clml.2017.06.001
DO - 10.1016/j.clml.2017.06.001
M3 - Article
C2 - 28807791
AN - SCOPUS:85028350315
SN - 2152-2650
VL - 17
SP - 684-695.e6
JO - Clinical Lymphoma
JF - Clinical Lymphoma
IS - 10
ER -