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

描述（由申请人提供）：由于慢性髓性白血病（CML）患者对伊马替尼（格列卫(R)）或类似的酪氨酸激酶抑制剂（TKIs）如达沙替尼和尼罗替尼完全有效的预后良好，CML的患病率估计在美国超过70,000例，预计到2050年将上升到180,000例。目前的建议是无限期地继续治疗，但这对患者和社会都是相当大的代价。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臂研究表明，22-61%的CML患者在TKI诱导的完全分子反应（MR 4.5）中，在停止TKI治疗后仍保持这种反应，并且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，因此建议在常规临床实践中监测停用TKI。此外，停药对健康状况的影响

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.