Stopping Tyrosine Kinase Inhibitors in CML Patients (Stop-TKIs)

CML 患者停用酪氨酸激酶抑制剂 (Stop-TKI)

• 批准号: 9132186
• 负责人: Ehab L Atallah
• 金额: $ 65.05万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-19 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9132186
• 关键词: Adverse effects; Age; Australia; Automobile Driving; Blood Tests; Cancer Center; Characteristics; Chronic Myeloid Leukemia; Clinical; Dasatinib; Data; Decision Making; Diarrhea; Europe; Family; Fatigue; Future; Gleevec; Health; Health Status; Healthcare Systems; Imatinib; Interdisciplinary Study; Interview; Left; Liquid substance; Maintenance; Measurement; Medicare; Mental Depression; Molecular; Monitor; Nausea; Outcome; Pain; Participant; Patient Monitoring; Patient Outcomes Assessments; Patient Schedules; Patient risk; Patients; Physicians; Policy Maker; Prevalence; Provider; Recommendation; Recurrence; Reporting; Risk; Skin; Sleep disturbances; Societies; Symptoms; System; Time; Transcript; Tyrosine Kinase Inhibitor; Uncertainty; United States Centers for Medicare and Medicaid Services; Work; arm; base; bcr-abl Fusion Proteins; clinical practice; cost; digital; experience; health related quality of life; improved; individual patient; leukemia; outcome forecast; response

DESCRIPTION (provided by applicant): With the favorable prognosis for patients with chronic myeloid leukemia (CML) who completely respond to imatinib (Gleevec(R)) or similar tyrosine-kinase inhibitors (TKIs) like dasatinib and nilotinib, the prevalence of CML is estimated at more than 70,000 patients in the U.S. and is projected to rise to 180,000 by 2050. The current recommendation is to continue therapy indefinitely, but this is at considerable cost to patients and society. TKIs are associated with reduced health status, including fatigue, nausea, depression, sleep disturbances, diarrhea, pain, fluid retention, and skin problems. Moreover, TKI therapies are among the most expensive, costing $92,000-138,000 per patient annually and place a financial burden on the U.S. health care system as well as on individual patients and their families. Small, single-armed studies from Europe and Australia suggest that 22-61% patients with CML in a TKI-induced complete molecular response (MR 4.5) maintain this response after discontinuation of TKIs, and patients whose CML recurred responded to reintroduction of TKI therapy. However, too little is known about the variables governing maintenance of MR 4.5 versus recurrence of CML to recommend TKI discontinuation with monitoring in routine clinical practice. Furthermore the impact of discontinuation on health status and the factors driving a patient's choice have never been studied, leaving patients and providers without guidance. The objective of the proposed Stopping Tyrosine Kinase Inhibitors in CML Patients (Stop TKIs) study is to improve the evidence for decision making regarding TKI discontinuation with monitoring in CML patients in stable MR 4.5. We will pursue 3 specific aims. Aim 1: To characterize the clinical characteristics associated with CML recurrence after TKI discontinuation. We will stop TKI therapy in 170 willing CML patients from 12 cancer centers and closely monitor them for 3 years for recurrence using standard as well as highly sensitive digital blood testing. We will develop a risk-scoring system to predict patients' risk of CML recurrence based on clinical characteristics and recommend an appropriate monitoring schedule for patients who have discontinued TKI therapy. Aim 2: To describe health status changes for patients who discontinue (and restart) TKIs. We will compare patients' reports of their health status while on TKI therapy to their reports of these same outcomes after discontinuation. For patients whose CML recurs, we will describe health status changes after TKI reintroduction. Aim 3: To explore how patients make the decision about TKI discontinue with monitoring. Using qualitative interviews with 20 patients, we will compare patients who are willing to stop TKIs with those who are unwilling to stop. We will evaluate how patients understand and weigh information about TKI discontinuation. The proposed work will be conducted by a multidisciplinary research team supported by a Patient Advisory Panel. At the conclusion of this work, we will have answered critical questions to support patients, physicians, and policy makers considering discontinuation of TKI therapy with monitoring for CML patients.

描述(申请人提供)：由于对伊马替尼(Gleevec(R))或类似的酪氨酸激酶抑制剂(TKIs)如达沙替尼和尼洛替尼完全有效的慢性髓系白血病(CML)患者预后良好，CML的患病率在美国估计超过7万名患者，预计到2050年将上升到18万人。目前的建议是无限期地继续治疗，但这对患者和社会来说是相当大的代价。TKI与健康状况下降有关，包括疲劳、恶心、抑郁、睡眠障碍、腹泻、疼痛、液体滞留和皮肤问题。此外，TKI疗法是最昂贵的疗法之一，每个患者每年的费用为92,000-138,000美元，这给美国医疗保健系统以及患者个人及其家人带来了经济负担。来自欧洲和澳大利亚的小型单臂研究表明，在TKI诱导的完全分子反应(MR 4.5)中，22-61%的CML患者在停止TKI治疗后保持这种反应，而CML复发的患者对重新引入TKI治疗有反应。然而，对于控制MR 4.5的维持与CML复发的变量知之甚少，建议在常规临床实践中停止TKI的监测。此外，停药对健康状况的影响 而且驱动患者选择的因素从未被研究过，使得患者和提供者没有得到指导。拟议的慢性粒细胞白血病患者停止酪氨酸激酶抑制物(STOP TKIS)研究的目的是改善在MR为4.5的稳定状态下CML患者停止TKI监测的决策依据。我们将追求3个具体目标。目的1：探讨TKI治疗后CML复发的临床特征。我们将停止对来自12个癌症中心的170名有意愿的CML患者进行TKI治疗，并使用标准和高灵敏度的数字血液测试对他们进行为期3年的密切监测，以确定复发情况。我们将开发一种风险评分系统，根据临床特征预测患者的CML复发风险，并为停止TKI治疗的患者推荐合适的监测计划。目的2：描述停止(和重新开始)TKIs患者的健康状况变化。我们将比较患者在接受TKI治疗时对其健康状况的报告与他们在停药后对相同结果的报告。对于CML复发的患者，我们将描述TKI重新引入后的健康状况变化。目的3：探讨患者如何做出停止监测的TKI决定。通过对20名患者的定性访谈，我们将比较愿意停止TKI和不愿停止TKIs的患者。我们将评估患者如何理解和权衡有关TKI停用的信息。拟议的工作将由一个多学科研究小组进行，并由患者咨询小组提供支持。在这项工作结束时，我们将回答一些关键问题，以支持考虑停止CML患者监测的TKI治疗的患者、医生和政策制定者。