From the Journals

Ibrutinib linked to hypertension in B-cell malignancies



The incidence and severity of hypertension was considerably higher in patients with B-cell malignancies treated with ibrutinib, according to a retrospective analysis.

Additionally, new or worsening hypertension was associated with a greater risk of major adverse cardiac events (MACE), including stroke, myocardial infarction, and cardiovascular-related death (hazard ratio, 2.17; 95% confidence interval, 1.08-4.38; P = .03).

“Despite ibrutinib’s benefits, cardiotoxicity has emerged as an increasingly important complication of this life-saving therapy,” Tyler Dickerson, PhD, of the Ohio State University, Columbus, and colleagues wrote in Blood.

The researchers retrospectively studied 562 consecutive patients with a lymphoid malignancy who received ibrutinib. Data was collected from patients treated at The Ohio State University’s Comprehensive Cancer Center during 2009-2016.

The mean age of study participants was 63.8 years, with a mean body mass index of 28.0 kg/m2. Most of the patients included in the analysis were men.

The team assessed rates of new or worsening hypertension, as well as rates of other MACE. The observed rates were compared with Framingham Heart Study–predicted incident-hypertension rates. The effects of various antihypertensive drugs on ibrutinib-linked hypertension were also evaluated.

After a median follow-up of 30 months, 78.3% of patients who received ibrutinib had new or worsening hypertension using a systolic blood pressure cutoff of 130 mm Hg. Of these, 84.8% of cases had an “at least probable association with ibrutinib,” they reported.

Among the 215 patients with no baseline hypertension, 71.6% developed hypertension while on ibrutinib, with a mean increase in systolic blood pressure of 13.4 mm Hg. Among the 347 patients with baseline hypertension, 82.4% experienced a worsening of their hypertension.

“This relationship remained even after accounting for ibrutinib dose, and was not attenuated by the use of any specific anti-hypertensive class,” the researchers wrote.

The researchers observed MACE among 93 patients. This included 84 patients with new or worsening hypertension and 9 patients with stable or no hypertension. Most MACE events were of at least probable ibrutinib association, the researchers reported.

Overall, the cumulative incidence of new hypertension at 1 year was 442 per 1,000 person-years in the current study. This value is 12.9-fold higher than the Framingham Heart Study risk–predicted rate of 34 per 1,000 person-years.

“Given the expected continued increase in ibrutinib use, further studies characterizing the mechanisms, treatment, and implications of [hypertension] during ibrutinib use are needed,” the researchers wrote.

The study was funded by the National Institutes of Health, the D. Warren Brown Family Foundation, the Four Winds Foundation, and the Connie Brown CLL Research Fund. The authors reported financial affiliations with Janssen, Pharmacyclics, and other companies.

SOURCE: Dickerson T et al. Blood. 2019 Oct 3. doi: 10.1182/blood.2019000840.

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