Jorge E Cortes1, Carlo Gambacorti-Passerini2, Dong-Wook Kim3, Hagop M Kantarjian4, Jeff H Lipton5, Amit Lahoti4, Moshe Talpaz6, Ewa Matczak7, Elly Barry8, Eric Leip8, Tim H Brümmendorf9, H Jean Khoury10. 1. University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: jcortes@mdanderson.org. 2. University of Milano-Bicocca, Monza, Italy. 3. Seoul St Mary's Hospital, Seoul, South Korea. 4. University of Texas M.D. Anderson Cancer Center, Houston, TX. 5. Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, Canada. 6. University of Michigan Comprehensive Cancer Center, Ann Arbor, MI. 7. Pfizer Inc, New York, NY. 8. Pfizer Inc, Cambridge, MA. 9. Universitätsklinikum RWTH Aachen, Aachen, Germany; Department of Internal Medicine II, Hubertus Wald Tumorzentrum University Cancer Center Hamburg, Hamburg, Germany. 10. Winship Cancer Institute of Emory University, Atlanta, GA.
Abstract
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.
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.
Authors: Jorge E Cortes; Jane F Apperley; Daniel J DeAngelo; Michael W Deininger; Vamsi K Kota; Philippe Rousselot; Carlo Gambacorti-Passerini Journal: J Hematol Oncol Date: 2018-12-27 Impact factor: 17.388
Authors: Carlo Gambacorti-Passerini; Jorge E Cortes; Jeff H Lipton; Hagop M Kantarjian; Dong-Wook Kim; Philippe Schafhausen; Rocco Crescenzo; Nathalie Bardy-Bouxin; Mark Shapiro; Kay Noonan; Eric Leip; Liza DeAnnuntis; Tim H Brümmendorf; H Jean Khoury Journal: Haematologica Date: 2018-05-17 Impact factor: 9.941