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
University of Texas M.D. Anderson Cancer Center, Houston, TX.
University of Milano-Bicocca, Monza, Italy.
Clin Lymphoma Myeloma Leuk. 2017 Oct;17(10):684-695.e6. doi: 10.1016/j.clml.2017.06.001. Epub 2017 Jun 17.
The purpose of the study was to assess renal function in patients with Philadelphia chromosome-positive leukemias receiving bosutinib or imatinib.
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.
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 m 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 m 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.
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.
本研究旨在评估接受博舒替尼或伊马替尼治疗的费城染色体阳性白血病患者的肾功能。
患者接受一线博舒替尼（n = 248）或伊马替尼（n = 251；III期试验），或二线及以后的博舒替尼（I/II期试验；n = 570）。评估不良事件（AE）以及估计肾小球滤过率（eGFR）和血清肌酐相对于基线的变化。
从最后一名患者首次给药至数据截止的时间≥48个月。接受二线及以后博舒替尼治疗的570例患者中有73例（13%）报告了肾脏不良事件，接受一线博舒替尼和伊马替尼治疗的患者中分别有22/248例（9%）和16/251例（6%）报告了肾脏不良事件。接受博舒替尼治疗的患者的eGFR随时间下降，与一线博舒替尼（26/248，10%）和伊马替尼（25/251，10%）相比，接受二线及以后博舒替尼治疗的患者中更多患者出现≥3b级eGFR下降（根据肾脏病饮食改良法，<45 mL/min/1.73 m²）（139/570，24%）；达到≥3b级eGFR的时间在接受二线及以后博舒替尼治疗的患者中最短。截至最后一次随访，接受二线及以后博舒替尼治疗的患者（74/139，53%）、一线博舒替尼治疗的患者（15/26，58%）和一线伊马替尼治疗的患者（15/25，60%）中，eGFR改善至≥45 mL/min/1.73 m²的比例相似。在一项回归分析中，博舒替尼与伊马替尼的一线治疗不是≥3b级eGFR的显著预测因素。
长期博舒替尼治疗与肾功能明显可逆性下降相关，其频率和特征与长期伊马替尼治疗时观察到的肾功能下降相似。具有≥3b级eGFR风险因素的患者应密切监测。
