Cardiovascular-related adverse events (CVD-AEs) and echocardiographic (Echo) changes with immunotherapy (IT): A real-world experience.

Abstract

11185 Background: Immune-checkpoint inhibitors (ICI) are standard of care for many solid tumors but are linked to cardiovascular adverse events (CVD-AEs). Real-world comparative data on CVD-AE incidence between IT & non-IT therapies are limited & no prior studies have evaluated longitudinal Echo changes in IT vs. non-IT patients. Methods: We conducted a retrospective cohort of 5,556 adults with solid malignancies at Cleveland Clinic Ohio (2010–2022). IT patients were compared to non-IT systemic therapy. Cancers included bladder (II-IIIA:476; IV:158), endometrial IV (157), gastric (II-III:797; IV:590), H&N IV (36), renal (III:88; IV:223), melanoma (45) & lung: NSCLC non-squamous (IIIB:206; IV:1609), NSCLC squamous (IIIB:182; IV:366) & SCLC IIIB-IV (623). Follow-up began at therapy start & continued until CVD-AE, last follow-up or death. Data were collected on demographics, CTCAE grade, management & outcomes. Incidence rates per 100 person-years (/100 Py) were estimated using Poisson regression, cumulative incidence (CIR) using Kaplan–Meier methods & adjusted hazard ratios (HRs) using time-dependent Cox models. Echo analyses (n = 418) compared baseline to follow-up studies using multinomial regression. Results: Of the cohort, 1,291 (23%) & 948 (17%) received 1st- & 2nd-line IT. Median age was 66; 38% were female, & 87% were White. ICI accounted for 99.9% of IT. During follow-up, 163 CVD-AEs occurred, including arrhythmias (n = 59), cardiac arrest (n = 35), myocarditis/heart failure (n = 21), pericarditis (n = 10) & acute coronary syndromes (NSTEMI n = 17, STEMI n = 15, unstable angina n = 5). Median follow-up was 14 months (CI 6-35). The CVD-AE CIRs were slightly higher in IT vs. non-IT groups (0.12 vs 0.11 /100 PY). The 4-year CIR was 5% in IT & 3.5% in non-IT (P = 0.4). In time-dependent Cox models, IT was not associated with a significant increase in composite CVD-AEs, though a borderline association with the composite of cardiac dysrhythmia & conduction disorders was observed (HR 1.43, P = 0.06). Echo analyses showed no association between IT & adverse changes in LV/RV systolic function (EF, GLS, TAPSE), pulmonary pressures or diastolic function (E/e’). In contrast, 1st-line IT was associated with increased odds of aortic root dilation (OR 2.95, p = 0.028), mitral valve sclerosis (OR 4.17, P = 0.02) & a trend toward mitral stenosis (OR 3.7, P = 0.05). Abnormal baseline Echo parameters remained the strongest predictors of future worsening. Conclusions: We found that IT was not associated with a significant rise in overall CVD-AEs or myocardial dysfunction, possibly reflecting less use of traditional cardiotoxic agents like anthracyclines. Novel associations with aortic root dilation & mitral valve sclerosis suggest vascular & structural remodeling effects. Findings highlight the need for long-term surveillance of structural heart changes beyond ejection fraction monitoring.