a Leukemia Service, Division of Hematologic Oncology , Department of Internal Medicine, Memorial Sloan Kettering Cancer Center , New York , NY , United States.
b AbbVie, Inc. , North Chicago , IL , United States.
Cancer Biol Ther. 2018 Jul 3;19(7):636-643. doi: 10.1080/15384047.2018.1449616. Epub 2018 Apr 30.
Novel therapies including kinase inhibitors (KI) have led to high and durable response in patients with chronic lymphocytic leukemia (CLL), however, some patients stop therapy. This study evaluates reasons for treatment changes among CLL patients who stopped KI in real-world practice. Sixty-nine US oncologists/hematologists provided patient-level data abstracted from charts of CLL adult patients who initiated a KI and later (1) switched to another anti-neoplastic regimen (Switched cohort), (2) discontinued the KI and remained untreated (Discontinued cohort), or (3) restarted the same KI after an interruption of ≥60 days (Restarted cohort). Demographics, clinical/treatment characteristics, and reasons for stopping, restarting, and switching the KI therapy were described. In the Switched cohort, reasons for stopping included disease progression (72.5%), low/no disease activity (3.9%), adverse event [AE]/ intolerance/comorbidity (15.7%), and planned cellular therapies (7.9%). In the Discontinued cohort, approximately half (46.0%) of patients stopped KI therapy because they were terminally ill/died, or were moved to best supportive care - these patients were older, had more severe disease, and high comorbidity burden. The other half (54.0% of patients) stopped due to low/no disease activity (24.0%), AEs/toxicity (12.0%), or patient-requested drug holiday (18.0%). In the Restarted cohort, the most common reasons for stopping KIs were patient request (37.3%), AEs/intolerance (31.4%), and economic reasons (10%). Patients restarted when disease progressed (60.8%) or when they recovered from the AE (33%). Reasons for KI stop and subsequent treatment patterns were varied and multifactorial, suggesting heterogeneous disease management and a need for more evidence around supporting strategies and physician education.
新型疗法，包括激酶抑制剂（KI），使慢性淋巴细胞白血病（CLL）患者获得了高且持久的应答，但部分患者停止了治疗。本研究评估了真实世界实践中停止 KI 治疗的 CLL 患者改变治疗方案的原因。69 名美国肿瘤学家/血液学家提供了从接受 KI 初始治疗后（1）转为另一种抗肿瘤方案（转换队列）、（2）停止 KI 且未接受治疗（停药队列）或（3）中断≥60 天后重新开始相同 KI（重新开始队列）的成年 CLL 患者图表中提取的患者水平数据。描述了人口统计学、临床/治疗特征以及停止、重新开始和转换 KI 治疗的原因。在转换队列中，停止治疗的原因包括疾病进展（72.5%）、低/无疾病活动（3.9%）、不良事件[AE]/不耐受/合并症（15.7%）和计划的细胞治疗（7.9%）。在停药队列中，大约一半（46.0%）的患者停止 KI 治疗，因为他们病危/死亡，或转为最佳支持治疗——这些患者年龄较大，疾病更严重，合并症负担更高。另一半（54.0%的患者）因低/无疾病活动（24.0%）、AE/毒性（12.0%）或患者要求药物假期（18.0%）停止治疗。在重新开始队列中，停止 KI 的最常见原因是患者要求（37.3%）、AE/不耐受（31.4%）和经济原因（10%）。当疾病进展（60.8%）或从 AE 中恢复（33%）时，患者重新开始治疗。KI 停止和随后的治疗模式各不相同且多因素，表明疾病管理存在异质性，需要更多支持策略和医生教育方面的证据。
