Cardiovascular Toxicities Associated With Ibrutinib

Area of Science:

• Pharmacovigilance
• Cardiovascular medicine
• Oncology

Background:

• Ibrutinib revolutionized B-cell malignancy treatment.
• A clinical trial indicated increased mortality with ibrutinib, suspected to be due to cardiovascular toxicities.
• Cardiovascular adverse drug reactions (CV-ADR) were not directly assessed in that trial.

Purpose of the Study:

• To identify and characterize cardiovascular adverse drug reactions (CV-ADR) associated with ibrutinib.
• To analyze the association between ibrutinib and CV-ADR, including fatal outcomes.

Main Methods:

• Utilized VigiBase, an international pharmacovigilance database.
• Performed disproportionality analysis using reporting odds ratios (ROR) and information component (IC).
• Assessed the significance of associations using IC025 > 0.

Main Results:

• Identified 303 ibrutinib-associated cardiovascular deaths.
• Found significant associations between ibrutinib and supraventricular arrhythmias (ROR: 23.1), heart failure (ROR: 3.5), and CNS events (ROR: 3.7).
• CV-ADR occurred early, with fatalities ranging from 10% to 20%.

Conclusions:

• Severe, sometimes fatal, cardiac events are associated with ibrutinib exposure.
• These CV-ADR must be considered in patient care and clinical trial design.
• Supraventricular arrhythmias combined with CNS events indicate a particularly poor prognosis.