# Major Bleeding with Ibrutinib in Chronic Lymphocytic Leukemia

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $73,806

## Abstract

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.

## Key facts

- **NIH application ID:** 10065995
- **Project number:** 1F32HL154519-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Neil Dhopeshwarkar
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $73,806
- **Award type:** 1
- **Project period:** 2020-08-15 → 2021-08-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065995

## Citation

> US National Institutes of Health, RePORTER application 10065995, Major Bleeding with Ibrutinib in Chronic Lymphocytic Leukemia (1F32HL154519-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10065995. Licensed CC0.

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