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Introduction: Preclinical studies indicate that the concurrent use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) may improve outcomes in broad groups of patients with cancer. There are limited data on the association between inhibitors of RAAS and outcomes among patients treated with immune checkpoint inhibitors (ICI). Hypothesis: RAAS inhibitors improve overall survival in patients treated with ICI. Methods: We performed a retrospective study of all patients treated with an ICI in a single academic network. Of 10,903 patients; 5,910 were on any anti-hypertensive medication. Of those on anti-hypertensive therapy, 3,426 were prescribed any RAAS inhibitor during ICI treatment and 2,484 were prescribed other anti-hypertensive medications. The primary outcome was overall survival in the entire cohort and in sub-groups by type of cancer. Results: Thoracic cancer (34%) and melanoma (16%) were the most common types of cancer and programmed cell death protein 1 inhibitor therapy was the most prescribed (76%). Those prescribed a RAAS inhibitor were older, more likely male and had more cardiovascular risk factors. In a Cox proportional hazard model, the concurrent use of RAAS inhibitors was associated with better overall survival (Figure). Among the different cancer types, there was a trend toward better overall survival among patients with gastrointestinal (Hazard Ratio (HR):0.82, [95% Confidence Interval (CI): 0.67-1.01], P=0.057) and genitourinary cancer (HR:0.81, [95% CI: 0.64-1.01], P=0.067). Conclusions: In this large retrospective study, patients who were concomitantly prescribed a RAAS inhibitor during ICI therapy had a better overall survival. The benefit of RAAS inhibitors was primarily noted among patients with gastrointestinal and genitourinary cancers. Prospective randomized trials are warranted to further evaluate and specify the benefit of RAAS inhibitors in cancer patients who receive ICI therapy.

Introduction: Immune checkpoint inhibitors (ICIs) treat an expanding range of cancers and the use of ICIs has been associated with an increase in atherosclerotic cardiovascular disease (ASCVD) events. The mechanisms involved in the increase in ASCVD with ICIs are incompletely understood. These same immune checkpoints targeted for cancer also regulate vascular function, yet there are no data testing the effect of ICIs on blood pressure. Hypothesis: Based on basic data on the role of these immune checkpoints in vascular function, we hypothesize that the use of ICIs would increase systolic and diastolic blood pressure. Methods: This was a single academic medical center study of 8,724 patients treated with an ICI. The primary analysis evaluated whether exposure to ICIs was associated with changes in blood pressure using repeated measures multivariate mixed linear regression models. The secondary analysis evaluated the effect of changes in blood pressure on all cause mortality using Cox proportional hazard models. Results: Of the 8,724 patients, 4,812 (55.2%) had a diagnosis of hypertension at ICI start. The average blood pressure at ICI start was 128.3±18.1/72.5±10.1mmHg. Among the entire cohort, there was a decrease of 2.9 mmHg in systolic blood pressure (95% CI: 2.70-3.02) after starting an ICI, and a drop of 1.6 mmHg (95% CI: 1.52-1.70) in diastolic blood pressure (adjusted, p Conclusions: Among a large cohort of patients, ICI therapy is associated with a drop in systolic and diastolic blood pressure. However, patients who had an increase of at least ≥20 mmHg in systolic blood pressure had lower risk of all-cause death.

Introduction: Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis. Hypothesis: We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications. Methods: Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death. Results: Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of >50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p Conclusions: Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.