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

Research output: Contribution to journalArticle

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

Fingerprint

Philadelphia Chromosome
Leukemia
Kidney
Glomerular Filtration Rate
Therapeutics
bosutinib
Diet Therapy
Imatinib Mesylate

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Cortes, J. E., Gambacorti-Passerini, C., Kim, D. W., Kantarjian, H. M., Lipton, J. H., Lahoti, A., ... 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

Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias. / Cortes, Jorge E.; Gambacorti-Passerini, Carlo; Kim, Dong Wook; Kantarjian, Hagop M.; Lipton, Jeff H.; Lahoti, Amit; Talpaz, Moshe; Matczak, Ewa; Barry, Elly; Leip, Eric; Brümmendorf, Tim H.; Khoury, H. Jean.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 17, No. 10, 10.2017, p. 684-695.e6.

Research output: Contribution to journalArticle

Cortes, JE, Gambacorti-Passerini, C, Kim, DW, Kantarjian, HM, Lipton, JH, Lahoti, A, Talpaz, M, Matczak, E, Barry, E, Leip, E, Brümmendorf, TH & Khoury, HJ 2017, 'Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias', Clinical Lymphoma, Myeloma and Leukemia, vol. 17, no. 10, pp. 684-695.e6. https://doi.org/10.1016/j.clml.2017.06.001
Cortes, Jorge E. ; Gambacorti-Passerini, Carlo ; Kim, Dong Wook ; Kantarjian, Hagop M. ; Lipton, Jeff H. ; Lahoti, Amit ; Talpaz, Moshe ; Matczak, Ewa ; Barry, Elly ; Leip, Eric ; Brümmendorf, Tim H. ; Khoury, H. Jean. / Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias. In: Clinical Lymphoma, Myeloma and Leukemia. 2017 ; Vol. 17, No. 10. pp. 684-695.e6.
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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.",
keywords = "Adverse events, Chronic myeloid leukemia, Renal toxicity, Tyrosine kinase inhibitors",
author = "Cortes, {Jorge E.} and Carlo Gambacorti-Passerini and Kim, {Dong Wook} and Kantarjian, {Hagop M.} and Lipton, {Jeff H.} and Amit Lahoti and Moshe Talpaz and Ewa Matczak and Elly Barry and Eric Leip and Br{\"u}mmendorf, {Tim H.} and Khoury, {H. Jean}",
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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

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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