Over a median of 30 months, 78.3% of patients developed new or worsening HTN, of which statistical analysis showed at least a probable association with ibrutinib. The mean increase in SBP was 5.2 mmHg (+/- 20.7 mmHg) with a 50% cumulative incidence of new or worsened HTN of 1.8 months.
Of those patients without baseline HTN (215 individuals, 38.2%), 71.6% of those patients developed new HTN while on ibrutinib, with a mean increase in SBP of 13.4 mmHg (+/- 20.1 mmHg). The time to 50% cumulative incidence was 4.2 months.
Patients with baseline HTN (347 individuals, 61.7%) had worsening HTN in 82.4% of patients. In addition, 37.6% of patients developed high-grade (3 or 4) HTN while on ibrutinib, of which 17.7% of those did not have baseline HTN. Lastly, 3.4% of all patients were hospitalized for HTN-related events, with only 3 patients requiring dose reduction or discontinuation secondary to uncontrolled HTN.
Univariate analysis concluded that increased body mass index (BMI), age, history of diabetes, CLL, and concurrent anthracycline use were associated with new or worsened HTN. Interestingly, there was no association between the ibrutinib dose and development of new or worsened HTN.
Multivariate analysis showed slightly different results, with CLL (vs non-CLL, HR, 1.64; 95% CI, 1.17-2.28, P =.004), CYP3A4 use (HR, 1.80; 95% CI, 1.25-2.59, P =.02) and baseline SBP all being associated with the development of HTN.
Initiation or increase in the number of anti-HTN medications was seen in 37.2% of ibrutinib patients, with 18% of patients requiring 3 or more agents. Patients were treated with several different classes of antihypertensives, however, no single class was associated with better HTN control. Conversely, the initiation of an anti-HTN agent was associated with lower risk of MACE (HR, 0.40; 95% CI, 0.24-0.66).