Cardiovascular Complications of Ibrutinib Therapy (CACIS)

Cardiovascular Complications of Ibrutinib Therapy: a Single-center Cohort Study

Ibrutinib, the first BTK inhibitor (BTKI) to be approved, improves progression-free survival (PFS) and overall survival (OS) over alternative therapies in relapsed/refractory and treatment-naive chronic lymphocytic leukemia (CLL). Ibrutinib has also been found to be effective in mantle cell lymphoma, Waldenström's macroglobulinemia and marginal zone lymphoma. However, ibrutinib treatment is associated with an increased risk of atrial fibrillation (AF), with an estimated 2-year AF rate of 16% in patients treated with ibrutinib during a median follow-up of 28 months. In most studies, AF was identified by reports as a treatment-related adverse event, and systematic screening for AF was not performed. As AF is often paroxysmal, the more intensive the screening, the higher the incidence. In a prospective cohort study of 53 patients treated with ibrutinib for CLL, patients were monitored by pulse palpation and ECG every 3 months. The cumulative incidence rate of ibrutinib-associated AF was 23% at 12 months and 38% at 2 years. The management of ibrutinib-associated AF is challenging due to difficulties in balancing the benefits of anticoagulation to mitigate the risk of stroke and the bleeding risk associated with ibrutinib. AF is a frequent reason for discontinuation of ibrutinib therapy, and can result in significant morbidity.

In addition to this arrhythmogenic effect, ibrutinib is also significantly associated with the onset or worsening of arterial hypertension. Finally, an increased risk of serious ventricular rhythm disorders has also been suggested by pharmacovigilance databases, but not yet confirmed by prospective clinical studies.

The study proposes a comprehensive cardiovascular approach, at baseline and during follow-up of patients on Ibrutinib, using innovative markers to anticipate patients most at risk of developing these cardiovascular effects, but also to detect them as early as possible in order to avoid the complications they may generate.

Study Overview

• Status: Terminated
• Conditions: Ibrutinib Treatment
• Intervention / Treatment: Other: ophthalmological examination; Biological: blood test

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • Chu Dijon Bourgogne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients will be identified by a doctor working in the hematology department of Dijon University Hospital during his or her regular medical check-up.

Description

Inclusion Criteria:

• Patients with an indication for ibrutinib treatment for hematologic reasons
• Patients aged 18 and over
• Patients who have given their free, written and informed consent to this study after being informed (or by the patient's representative if the patient is unable to express his or her consent).

Exclusion Criteria:

• Person not affiliated to national health insurance
• Patient under legal protection (curatorship, guardianship)
• Patient subject to a safeguard of justice measure
• Pregnant, parturient or breast-feeding women
• Previous treatment with ibrutinib
• Follow-up planned in another center
• History of atrial fibrillation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patient; Patients with an indication for ibrutinib treatment for hematologic reasons	Other: ophthalmological examination; OCT-retinal angiography At inclusion, 3 months and 6 months; Biological: blood test; a 2-mL tube of blood will be taken to test for blood markers predisposing to cardiovascular complications. At inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
rate of patients developing atrial fibrillation (AF)	Compare the values of selected biomarkers between patients who have developed AF and patients without AF	12 months after introduction of ibrutinib

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Actual): August 5, 2025
• Study Completion (Actual): August 5, 2025

Study Registration Dates

• First Submitted: July 3, 2023
• First Submitted That Met QC Criteria: July 3, 2023
• First Posted (Actual): July 11, 2023

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Hematologic Tests
• Other Study ID Numbers: ROBERT AOI 2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No