A Deeper Look Into Hypertension and Cardiovascular Toxicity Symptoms for Patients Treated With Ibrutinib

In a recent study, Max Gordon, MD, from the Division of Cancer Medicine at the University of Texas MD Anderson Cancer Center, and colleagues investigated the long-term impacts that patients had after ibrutinib treatment for chronic lymphocytic leukemia (CLL) (Cancer. 2023;129(14): 2192-2200. doi:10.1002/cncr.34787). They specifically focused on whether there was a relationship between hypertension and cardiovascular symptoms. This study followed up with patients 5 years after ibrutinib treatment.

First, Dr Gordon and colleagues assessed blood pressure, cardiovascular disease, progression of disease, and death, which can all be indicators of hypertension or cardiovascular toxicities. They identified patients that had hypertension by previous diagnosis before starting ibrutinib, and their definition of hypertension was based on the American College of Cardiology/American Heart Association guidelines. They performed a univariate logistic regression analysis to find a connection between these patient characteristics and the occurrence of new or worsened hypertension. Competing risk was used to evaluate the rate of hypertensive outcomes per patient and patient survival was calculated with the Kaplan-Meier method. The primary outcome in this study was new or worse hypertension for patients with CLL that were treated with ibrutinib. The secondary outcome was cardiovascular and renal complications in patients with CLL.

In this study, 300 patients with CLL that were treated with ibrutinib were included. The median age of patients at the beginning of treatment was 65 years old. Of these patients:

• 70% identified as men
• 88% were Caucasian
• 69% had hypertension at baseline
• 47% were on antihypertensive medication
• 88% had relapsed or refractory CLL
• 68.5% experienced new onset hypertension
• 38% experienced worsening hypertension
• 16.9% had systolic blood pressure higher than 160 mm Hg or diastolic blood pressure higher than 100 mm Hg

The researchers found that hypertension was reversible in patients who stopped ibrutinib treatment. A connection between hypertension and cardiovascular toxicities was not found in the study. They did find that characteristics such as older age, male sex, tobacco intake, and chronic kidney disease contributed to a higher likelihood of hypertension development while on ibrutinib and post-ibrutinib treatment. They also analyzed the risk of developing hypertension after starting ibrutinib treatment. In the 94 patients that did not have hypertension before the trial, 68.5% of patients had the potential to develop hypertension 5 years later. For the 204 patients that already had hypertension, there was a 38% chance that it would worsen. After 5 years, 61% of patients discontinued ibrutinib because of adverse events such as cardiovascular issues or secondary cancers. Patients also discontinued use because of disease progression. Results for discontinuation were similar regardless of whether a patient had hypertension before or after ibrutinib treatment and whether they had previously experienced a cardiovascular event.

Ultimately, Dr Gordon and colleagues determined that the hypertension commonly found in patients with CLL who receive ibrutinib as a part of their treatment plan is manageable and does not pose a risk to the development of cardiovascular toxicities. With the exception of chronic kidney disease, baseline cardiovascular disease was not found to affect ibrutinib-related hypertension, and hypertension was not associated with major adverse cardiovascular events or patient survival.