Major Bleeding with Ibrutinib in Chronic Lymphocytic Leukemia

依鲁替尼治疗慢性淋巴细胞白血病的大出血

• 批准号: 10065995
• 负责人: Neil Dhopeshwarkar
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2021-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10065995
• 关键词: Active Learning; Address; Adverse drug event; Agammaglobulinaemia tyrosine kinase; Age; Anticoagulants; Atrial Fibrillation; Award; B-Lymphocytes; Benefits and Risks; Blood; Bone Marrow; Cessation of life; Chlorambucil; Chronic Lymphocytic Leukemia; Clinical; Clinical Trials; Cohort Studies; Country; Data; Databases; Diagnosis; Doctor of Philosophy; Effectiveness; Elderly; Epidemiology; Equilibrium; Event; Exclusion; Exposure to; Fellowship; Frequencies; Funding; Healthcare; Hematologic Neoplasms; Hematological Disease; Hemorrhage; Heterogeneity; Incidence; Individual; Interruption; Knowledge; Life; Measures; Medical; Mentors; Methods; Oral; Patients; Pharmaceutical Preparations; Pharmacoepidemiology; Population; Prevention; Public Health; Refractory; Regimen; Relapse; Research; Risk; Risk Factors; Safety; Source; Spleen; Time; Training; Transfusion; Tyrosine Kinase Inhibitor; United States; United States Dept. of Health and Human Services; Work; anticancer treatment; blood treatment; career; chemotherapy; clinical decision-making; clinical practice; comorbidity; comparative; economic cost; experience; high risk; improved; improved outcome; leukemia; leukemia treatment; lymph nodes; new therapeutic target; novel; novel therapeutics; prevent; programs; response; rituximab; safety study; targeted treatment; treatment effect; treatment strategy

Project Summary Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in western countries, with an estimated 20,720 new cases and 3,930 deaths from CLL in 2019 in the United States. Recently, novel targeted therapies have significantly changed CLL treatment. Specifically, ibrutinib dramatically improves outcomes in both treatment-naïve and previously-treated CLL patients. Although ibrutinib has a favorable safety profile compared to chemotherapy, bleeding occurs in ~50% of treated individuals. Major bleeding (typically defined as fatal, life-threatening, or transfusion-requiring) was relatively uncommon in clinical trials, with 4-8% of ibrutinib-treated patients experiencing a major bleeding event. However, due to the exclusion of patients with comorbidities and other bleeding risk factors, these findings may underestimate the frequency of major- bleeding in real-world clinical practice. Currently, major bleeding is not well characterized in real-world ibrutinib users, as few studies have measured the incidence of ibrutinib-associated major bleeding in real-world populations. Furthermore, many ibrutinib-treated CLL patients may be concomitantly using oral anticoagulants (OACs) to prevent life-threatening thromboembolic events caused by comorbid medical conditions and ibrutinib-related complications. The frequency of bleeding events is likely to be higher with ibrutinib and OACs taken together than either drug alone. However, this remains unconfirmed as there is limited data on patients using this combination. Without knowledge of ibrutinib-associated major bleeding, clinicians must make a difficult decision of whether to treat high-risk patients with ibrutinib. This study aims to measure the comparative risk of major bleeding associated with ibrutinib versus bendamustine+rituximab, a widely used alternative CLL regimen, in CLL patients and in CLL patients concomitantly taking OACs. This aim will be addressed by conducting two cohort studies in a nationally-represented commercially-insured population. This work will fill an important gap of knowledge in ibrutinib’s major bleeding risk and may improve treatment strategies for CLL patients susceptible to ibrutinib’s bleeding effects. The accompanying training plan consists of both didactic training as part of a PhD program in epidemiology, and experiential learning opportunities focused on the use of electronic healthcare data for pharmacoepidemiologic research. This fellowship award will provide essential support to enable the trainee’s pursuit of a career as an independently-funded academic pharmacoepidemiologist focused on studying the prevention and treatment of blood disorders and complications.

项目摘要 慢性淋巴细胞性白血病（CLL）是西方国家最流行的白血病， 美国2019年CLL新增病例20,720例，死亡3,930例。最近，新的靶向治疗 显著改变了CLL治疗。具体来说，伊布替尼显著改善了两种疾病的结局， 初治和既往接受过治疗的CLL患者。尽管伊曲替尼具有良好的安全性， 与化疗相比，约50%的治疗个体发生出血。大出血（通常定义为 致命的、危及生命的或需要输血的）在临床试验中相对少见， 伊匹替尼治疗患者发生大出血事件。然而，由于排除了患有 合并症和其他出血风险因素，这些发现可能低估了重大出血的频率， 在现实世界的临床实践中，目前，在真实世界的伊布替尼中，大出血的特征尚不明确 使用者，因为很少有研究测量了真实世界中伊匹替尼相关大出血的发生率 人口。此外，许多接受伊鲁替尼治疗的CLL患者可能同时使用口服抗凝剂 （OAC），以预防由合并症引起的危及生命的血栓栓塞事件， 伊替尼相关并发症。使用伊鲁替尼和OAC时出血事件的频率可能更高 比单独服用任何一种药物都要好。然而，由于患者数据有限，这一点尚未得到证实。 使用这种组合。在不了解伊匹替尼相关大出血的情况下，临床医生必须对 难以决定是否用伊布替尼治疗高危患者。本研究旨在衡量 伊曲替尼与苯达莫司汀+利妥昔单抗相关的大出血风险比较， 替代CLL方案，在CLL患者和伴随使用OAC的CLL患者中。这一目标将是 通过在全国有代表性的商业保险人群中进行两项队列研究来解决。这 这项工作将填补对伊布替尼主要出血风险的重要认识空白，并可能改善治疗。 CLL患者易受伊鲁替尼出血影响的策略。附带的培训计划包括 作为流行病学博士课程的一部分， 专注于使用电子医疗保健数据进行药物流行病学研究。这个奖学金 将提供必要的支持，使学员能够追求职业生涯作为一个独立资助的学者 药物流行病学家专注于研究血液疾病的预防和治疗， 并发症