Division of Oncology and Hematology, Department of Internal Medicine, Konkuk University School of Medicine, Chungju, Korea.
Center of Biomedical Data Science, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Clin Lymphoma Myeloma Leuk. 2019 Nov;19(11):735-743.e2. doi: 10.1016/j.clml.2019.08.009. Epub 2019 Aug 29.
Tyrosine kinase inhibitors (TKIs) improve the survival rate of patients with chronic myeloid leukemia (CML). However, elderly patients often experience adverse events and require dose adjustments, leading to dose interruptions or treatment discontinuation. We therefore investigated TKI dosing patterns and subsequent outcomes in elderly CML patients.
Using the National Health Information Database, we identified patients with CML aged ≥ 70 years who were prescribed TKIs (imatinib, dasatinib, nilotinib, or radotinib) during 2007-2013. Data on age, sex, prescribed medication, and date of death were extracted.
Among the 378 patients, the median age was 75 (range, 70-92) years; the median follow-up period was 53 (range, 1-133) months. Imatinib, dasatinib, nilotinib, and radotinib were prescribed to 324 (85.7%), 110 (29.1%), 93 (24.6%), and 15 (4.0%) patients, respectively. In 42 patients (12.2%), the initial dose was lower than the recommended dose for chronic-phase CML. At last follow-up, 249 patients (65.9%) were receiving a reduced dose. The mean ± standard deviation dose densities of imatinib, dasatinib, nilotinib, and radotinib were 207 ± 121.6, 29 ± 26.7, 235 ± 197, and 123 ± 95.4 mg/day, respectively. The estimated 5-year overall survival probability was 61.0%. Initial TKI dose or dose reduction within first year did not affect the overall survival (P = .0571 and .1826, respectively).
Dose reduction was observed in 65.9% of the patients at their last visit; except for imatinib, TKI dose densities were < 50% of the recommended dose for the chronic phase. Therefore, the recommended TKI doses might be too high for elderly patients with CML.
酪氨酸激酶抑制剂（TKIs）可提高慢性髓性白血病（CML）患者的生存率。然而，老年患者常发生不良反应，需要调整剂量，导致剂量中断或停药。因此，我们研究了老年 CML 患者的 TKI 给药方案和后续结局。
我们使用国家健康信息数据库，确定了在 2007 年至 2013 年期间接受 TKI（伊马替尼、达沙替尼、尼洛替尼或拉地替尼）治疗的年龄≥70 岁的 CML 患者。提取了年龄、性别、处方药物和死亡日期的数据。
在 378 名患者中，中位年龄为 75（范围：70-92）岁；中位随访时间为 53（范围：1-133）个月。伊马替尼、达沙替尼、尼洛替尼和拉地替尼分别被处方给 324（85.7%）、110（29.1%）、93（24.6%）和 15（4.0%）名患者。在 42 名患者（12.2%）中，初始剂量低于慢性期 CML 的推荐剂量。最后一次随访时，249 名患者（65.9%）接受了降低剂量。伊马替尼、达沙替尼、尼洛替尼和拉地替尼的平均±标准偏差剂量密度分别为 207±121.6、29±26.7、235±197 和 123±95.4 mg/天。估计的 5 年总生存率为 61.0%。初始 TKI 剂量或第一年的剂量降低均不影响总生存率（P=0.0571 和 0.1826）。
最后一次就诊时，65.9%的患者进行了剂量降低；除伊马替尼外，TKI 剂量密度均低于慢性期的推荐剂量。因此，推荐的 TKI 剂量可能对老年 CML 患者过高。
