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: 8818837
• 负责人: Ehab L Atallah
• 金额: $ 78.55万
• 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/8818837
• 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 Status; Healthcare Systems; Imatinib; Individual; Interdisciplinary Study; Interview; Left; Liquid substance; Maintenance; Measurement; Medicare; Mental Depression; Molecular; Monitor; Nausea; Outcome; Pain; Participant; Patient Monitoring; Patient Outcomes Assessments; Patient Schedules; 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; leukemia; outcome forecast; public health relevance; 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（由申请人提供）：由于对伊马替尼（Gleevec（R））或类似的酪氨酸激酶抑制剂（TKI）如达沙替尼和尼洛替尼完全应答的慢性粒细胞白血病（CML）患者预后良好，CML的患病率估计在美国超过70，000例患者，预计到2050年将上升至180，000例。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成本。TKI与健康状况下降相关，包括疲劳、恶心、抑郁、睡眠障碍、腹泻、疼痛、液体潴留和皮肤问题。此外，TKI疗法是最昂贵的疗法之一，每位患者每年花费92，000 - 138，000美元，给美国医疗保健系统以及患者个人及其家庭带来了经济负担。来自欧洲和澳大利亚的小型单组研究表明，22-61%的TKI诱导完全分子学缓解（MR 4.5）的CML患者在停用TKI后仍保持这种缓解，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维持与CML复发的变量知之甚少，无法在常规临床实践中建议停用TKI并进行监测。此外，停药对健康状况的影响 而驱动病人选择的因素从未被研究过，这使得病人和医疗服务提供者都没有得到指导。拟定的CML患者停用酪氨酸激酶抑制剂（停用TKI）研究的目的是改善在MR 4.5稳定的CML患者中进行TKI停药监测的决策证据。我们将实现三个具体目标。目的1：描述TKI停药后与CML复发相关的临床特征。我们将在12个癌症中心的170名愿意接受TKI治疗的CML患者中停止TKI治疗，并使用标准和高度敏感的数字血液检测密切监测他们3年的复发情况。我们将开发一个风险评分系统，以根据临床特征预测患者的CML复发风险，并为停止TKI治疗的患者推荐适当的监测计划。目的2：描述停止（和重新开始）TKI的患者的健康状况变化。我们将比较患者在TKI治疗期间的健康状况报告与停药后相同结局的报告。对于CML复发的患者，我们将描述重新引入TKI后的健康状况变化。目的3：探讨患者如何在监测下做出停止TKI的决定。使用20例患者的定性访谈，我们将比较愿意停止TKI的患者与不愿意停止TKI的患者。我们将评估患者如何理解和权衡有关TKI停药的信息。拟议的工作将由一个多学科研究小组进行，并得到患者咨询小组的支持。在这项工作结束时，我们将回答关键问题，以支持患者，医生和政策制定者考虑停止TKI治疗并监测CML患者。