Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Pediatrics, University of Washington, Seattle Children's Hospital, Seattle, WA, USA.
Leuk Lymphoma. 2021 May;62(5):1203-1210. doi: 10.1080/10428194.2020.1855340. Epub 2020 Dec 7.
With tyrosine kinase inhibitor (TKI) therapy, chronic myelogenous leukemia (CML) is now a chronic disease. CML patients treated with TKIs ( = 1200) were identified from the OptumLabs Data Warehouse (de-identified claims and electronic health records) between 2000 and 2016 and compared with a non-cancer cohort ( = 7635). The 5-year cumulative incidence of all organ system outcomes was significantly greater for the TKI versus non-cancer group. In the first year, compared with imatinib, later generation TKIs were associated with primary infections (hazard ratios [HR] 1.43, 95% CI 1.02-2.00), circulatory events (HR 1.15, 95% CI 1.01-1.31), and skin issues (HR 1.43, 95% CI 1.13-1.80); musculoskeletal and nervous system/sensory issues were less common (HRs 0.83-0.84, < 0.05). Increased risk of infections, cardiopulmonary and skin issues associated with later generation TKIs persisted in subsequent years. In this real-world population, TKI therapy was associated with a high burden of adverse events. Later generation TKIs may have greater toxicity than imatinib.
随着酪氨酸激酶抑制剂(TKI)治疗的出现,慢性髓细胞白血病(CML)现在已成为一种慢性疾病。从 2000 年到 2016 年,通过 OptumLabs 数据仓库(去识别索赔和电子健康记录)确定了 1200 名接受 TKI 治疗的 CML 患者,并与非癌症队列(7635 名)进行了比较。与非癌症组相比,TKI 组所有器官系统结局的 5 年累积发生率显著更高。在第一年,与伊马替尼相比,后一代 TKI 与原发性感染(危险比 [HR] 1.43,95%置信区间 [CI] 1.02-2.00)、循环系统事件(HR 1.15,95%CI 1.01-1.31)和皮肤问题(HR 1.43,95%CI 1.13-1.80)相关;肌肉骨骼和神经系统/感觉问题则不太常见(HRs 0.83-0.84, < 0.05)。与后一代 TKI 相关的感染、心肺和皮肤问题的风险增加在随后的几年中持续存在。在这个真实世界的人群中,TKI 治疗与不良事件负担高有关。与伊马替尼相比,后一代 TKI 可能具有更大的毒性。