Abstract 017: Dual Immune Checkpoint Inhibitor Therapy Is Associated With Increased Blood Pressure In Melanoma Patients

Abstract

Background: Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer therapy through activating immune cells to overcome tumor immune evasion. Increasing evidence suggests that adaptive immune cells play an important role in blood pressure elevations in the pathogenesis of hypertension. Whether ICI therapy enhances blood pressure remains unclear. Methods: We performed a retrospective cohort study of patients with advanced melanoma treated with ICIs in a single academic center. Baseline and 2-year blood pressure readings after initiation of ICI therapy were compared. To determine the relationship between the demographic and treatment variables and the change in blood pressure at two years, a multivariable linear regression model was used. Results: A total of 259 individuals were identified with 2-year follow-up. Of the entire cohort, 31% were treated with nivolumab, 47% with pembrolizumab, and 23% with ipilimumab and nivolumab combination therapy. In the total cohort, ICIs were not associated with significant changes in systolic (SBP) or diastolic (DBP) blood pressure at 2 years compared to baseline (132.2 mmHg vs . 133.2 mmHg, p=0.17, and 78.6 vs . 78.1 mmHg, p=0.50, respectively). There were also no statistically significant changes in SBP or DBP in patients treated with nivolumab or pembrolizumab alone. However, in those treated with ipilimumab and nivolumab as combination therapy, SBP increased by 5.5 mmHg (128.2 vs. 133.7 mmHg, p=0.005). After adjusting for age, sex, weight, ICI type and duration, steroid and tyrosine kinase inhibitor use, and antihypertensive medication use at baseline and 2-years, combination therapy with ipilimumab and nivolumab remained a significant predictor of SBP change at two years. Holding the baseline SBP constant, the predicted SBP was 6.2 mmHg (95% CI 0.08 - 12.0 mmHg, p=0.047) higher for combined therapy than nivolumab alone. Conclusions: Patients who received combination ICI therapy had a higher SBP compared to those treated with single agent therapy. These findings suggest immune cell activation with ICI therapy contributes to blood pressure elevations and that close follow-up of blood pressure is needed in cancer survivors, particularly those previously treated with combination ICI therapy.