Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias

Jorge E. Cortes, Carlo Gambacorti-Passerini, Dong Wook Kim, Hagop M. Kantarjian, Jeff H. Lipton, Amit Lahoti, Moshe Talpaz, Ewa Matczak, Elly Barry, Eric Leip, Tim H. Brümmendorf, H. Jean Khoury

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13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)684-695.e6
JournalClinical Lymphoma, Myeloma and Leukemia
Volume17
Issue number10
DOIs
StatePublished - Oct 2017
Externally publishedYes

Keywords

  • Adverse events
  • Chronic myeloid leukemia
  • Renal toxicity
  • Tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Cortes, J. E., Gambacorti-Passerini, C., Kim, D. W., Kantarjian, H. M., Lipton, J. H., Lahoti, A., Talpaz, M., Matczak, E., Barry, E., Leip, E., Brümmendorf, T. H., & Khoury, H. J. (2017). Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias. Clinical Lymphoma, Myeloma and Leukemia, 17(10), 684-695.e6. https://doi.org/10.1016/j.clml.2017.06.001