Combination Therapies Provide Optimal Hypertensive Control in Patients Taking Ibrutinib

Patients who take ibrutinib (Imbruvica; Pharmacyclics/Janssen) and experience new or worsening hypertension are best treated with combination anti-hypertensive therapies, according to a new report.

However, the report also found that the optimal combinations of antihypertensive drugs differ depending on whether the patient’s hypertension (HTN) emerged before or after beginning ibrutinib. The study was published in Blood Advances.

Blood pressure measurement | Image credit: interstid - stock.adobe.com

Corresponding author Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center and the University of Washington School of Medicine, and colleagues, noted that ibrutinib is widely used to treat a variety of lymphoid malignancies, including chronic lymphocytic leukemia and marginal zone lymphoma. However, a high percentage of patients taking Bruton’s tyrosine kinase inhibitors (BTKi’s) experience hypertension. One study found more than three-quarters of patients taking ibrutinib experienced new or worsening hypertension over a median of 30 months, they noted.

Yet, there is relatively little in the way of clarity about which anti-hypertensive strategies are most effective, the authors said.

“While standard antihypertensive (anti-HTN) medications are commonly employed to treat HTN in patients taking a BTKi, guidance on the optimal class of anti-HTN medication is lacking with some experts suggesting these drugs should be chosen according to patients’ comorbidities or so as to avoid pharmacokinetic interactions between medications,” Shadman and colleagues wrote.

The investigators decided to examine the medical records of 196 patients who were treated with a BTKi and one or more hypertensive medications for a period of at least 3 months between 2014 and 2018. The patients were treated at one of 14 medical centers in the United States, and they had a median age of 67. Almost all of the patients (93%) included in the study were White, and 71% of participants were male. Most of the patients (118) had hypertension prior to beginning BTKi treatment; the remaining 78 developed hypertension after starting treatment with a BTKi. Though the study included patients on any BTKi, 90% of those included in the study were taking ibrutinib, mostly because newer BTKis were not yet available for most of the study’s time frame.

The research analyzed which categories of anti-hypertensive therapy the patients were prescribed and the outcomes of those treatments, assessed in terms of the average reduction in mean arterial pressure (MAP).

The data suggested that, in patients with prior hypertension, the most effective treatment strategy was a combination of beta blockers and hydrochlorothiazide (mean MAP reduction of –5.05 mmHg; 95% CI –10.0 to –0.0596; P = 0.047). In patients with de novo hypertension, the combination of ACE inhibitors or angiotensin receptor blockers (ARBs) with hydrochlorothiazide appeared optimal (–5.47 mmHg; 95% CI –10.9 to –0.001; P = 0.05). The authors said these combinations also yielded the highest number of normotensive MAPs.

Shadman and colleagues said the new research is important because hypertension can lead to an increased risk of life-threatening events such as myocardial infarction and stroke. They noted that their study suggests drug combinations are most effective, a finding in line with outcomes for hypertension patients in the general population of people with hypertension.

The investigators cautioned that their study was retrospective in nature; they said larger prospective studies should be launched to confirm their findings. They said it will also be important to analyze whether patients who experienced de novo hypertension while on a BTKi saw a change in their hypertension after reducing or discontinuing their BTKi. The authors also acknowledged that physicians treating patients with BTKi-related hypertension will need to consider any patient comorbidities when making treatment recommendations.

Still, Laura Samples, MD, the study’s first author, said in a press release that the report highlights the importance of keeping hypertension top-of-mind when prescribing ibrutinib.

“Given that increased blood pressure is a ‘class effect’ of treatment with BTKis, both doctors and patients need to be aware of this risk and patients’ blood pressure should be monitored regularly so that treatment can begin immediately when an increase is detected,” said Samples, who, like Shadman, is a physician with the Fred Hutchinson Cancer Center and the University of Washington School of Medicine.

Reference

Samples L, Voutsinas JM MPH, Fakhri B, et al. Hypertension Treatment in Patients Receiving Ibrutinib: A Multicenter Retrospective Study. Blood Adv. Published online February 2, 2024. doi:10.1182/bloodadvances.2023011569