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-nave 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.
Ibrutinib is a novel anti-cancer treatment that is highly efficacious in the treatment of chronic lymphocytic leukemia (CLL). Although bleeding occurs frequently in ibrutinib-treated patients, major bleeding (typically defined as fatal, life-threatening, or transfusion-requiring) associated with ibrutinib in real-world clinical practice is not well characterized. 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 exposed to oral anticoagulants.
