Ibrutinib Linked to Increased Hypertension Risk in Study

More than half of the patients who took the targeted therapy ibrutinib, used to treat mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and other blood disorders, saw increased blood pressure within 6 months of starting the drug, according to a study published this week in Blood, the official journal of the American Society of Hematology.

Ibrutinib, a kinase inhibitor sold as Imbruvica, caused the onset or worsening of hypertension in patients who had this complication regardless of the prescribed dose. The analysis is the first that links ibrutinib-related hypertension to an elevated risk of heart problems, including atrial fibrillation. Those who developed hypertension were twice as likely to experience heart problems like arrythmia as those who did not have high blood pressure.

“This study provides a more clear picture of the extent of hypertension development among patients taking ibrutinib, while allowing us to tease out what ibrutinib-related hypertension means in the long run for other cardiovascular events and survival,” Daniel Addison, MD, of the Ohio State Wexner Medical Center and senior author, said in a statement. “Overall, both the magnitude and level of hypertension that developed was higher than previously thought and appears to portend a higher risk of other cardiac events.”

Fortunately, the risk associated with ibrutinib is relatively simple to treat: When patients who saw their blood pressure rise were given medication to treat it, they saw a 60% reduction in adverse cardiovascular events.

Addison emphasized that ibrutinib is a life-saving therapy that has become a well-known weapon in treating more than 10 different types of blood cancer. The drug works by blocking the protein Bruton’s tyrosine kinase, which can allow cancer cells to multiply. Assessing how cancer therapies affect cardiovascular outcomes, both short term and long term, and treating patients for these effects, is an increasingly important part of team-based care.

“Accordingly, we need to find the best ways to manage high blood pressure and protect against other heart-related issues,” he said.

Researchers reviewed medical records of 562 patients treated with ibrutinib for B-cell cancers at the Ohio State University Comprehensive Cancer Center between 2009 to 2016. Most patients were male with CLL; the average age was 64 years. The first looked at whether they patients developed hypertension or saw hypertension become worse; then, they examined whether other cardiovascular problems followed this increase.

Of note, the cutoff for diagnosing hypertension was a systolic blood pressure of 130 mm Hg, which had to be recorded on consecutive visits within 3 months. This stricter guideline was adopted in November 2017 by the American College of Cardiology and the American Heart Association. Previously, the cutoff for systolic BP was 140 mm Hg.

Nearly 72% of ibrutinib users were diagnosed with onset hypertension over median follow-up of 30 months after starting the drug. Researchers reported there was evidence that blood pressure rose quickly after therapy began among those who not have hypertension before they started treatment.

The rate of new hypertension was 54% within 6 months; the average systolic blood pressure increase was 13 mm Hg. This increase far outpaced predictive models; high blood pressure was 13 times higher than would be expected in patients of similar age and heart conditions who were not taking ibrutinib.

Among those taking ibrutinib, 19.1% of those with worsened blood pressure had cardiovascular complications, compared with 8.2% who did not see their blood pressure rise.

Reference

Dickerson T, Wiczer T, Waller A, et al. Hypertension and incident cardiovascular events following ibrutinib initiation [published online October 3, 2019]. Blood. doi: 10.1182/blood.2019000840.