Ibrutinib Is Associated With Increased Cardiovascular Events and Major Bleeding in Older CLL Patients

Area of Science:

• Oncology
• Hematology
• Pharmacovigilance

Background:

• Early ibrutinib trials noted bleeding and atrial fibrillation (AF) risks in younger chronic lymphocytic leukemia (CLL) patients.
• Limited data exists on these adverse events in older CLL patients and their association with stroke risk.

Purpose of the Study:

• To compare the incidence of stroke, AF, myocardial infarction, and bleeding in CLL patients treated with ibrutinib versus those not treated with ibrutinib.
• To assess the association between ibrutinib treatment and adverse events in an older CLL patient cohort using a linked SEER-Medicare database.

Main Methods:

• Utilized a linked SEER-Medicare database to identify CLL patients.
• Calculated incidence rates of adverse events for both ibrutinib-treated and untreated groups.
• Employed inverse probability weighted Cox proportional hazards regression to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for ibrutinib's association with adverse events.

Main Results:

• Among 4,958 CLL patients (median age 77 years), 6% received ibrutinib.
• Ibrutinib treatment was associated with a 1.91-fold increased risk of stroke, 3.65-fold increased risk of AF, and 4.92-fold increased risk of bleeding.
• A significantly higher risk of major bleeding (7.49-fold) was observed in the ibrutinib group compared to non-ibrutinib users.

Conclusions:

• Ibrutinib treatment in older CLL patients is linked to elevated risks of stroke, AF, and bleeding.
• The observed risk of major bleeding is greater than previously reported.
• Emphasizes the critical role of surveillance registries in identifying novel safety signals for cancer therapies.