Abstract 10520: Emerging Cardiovascular Side Effects of Selective and Non-Selective Immunotherapies in Cancer Patients: 2021 Results from the Global WHO Database

Abstract

Introduction: Immune checkpoint inhibitors (ICIs), and adoptive cell transfer (ACT) - which involves collecting and using patient’s own immune cells to treat their cancer, are two rapidly emerging therapeutic modalities for various advanced stage cancers. Emerging cardiovascular side effects of ICIs and ACTs are currently being recognized. Objective: We analyzed the newly reported side-effect profiles of FDA-approved ICIs (anti-CTLA-4, anti-PD-1 and anti-PD-L1) and ACTs (also known as CAR-T therapy). Methods: We utilized the global data available in VigiBase®, World Health Organization’s global database for adverse drug reactions (ADRs), maintained by the Uppsala Monitoring Centre. We extracted information on reports of suspected ADRs, also called Individual Case Safety Reports (ICSRs). ICSRs of ICI and ACT therapy on cardiovascular system were extracted, and the side effect profile of the two groups of immunotherapies were systematically analyzed. Results: Based on the records obtained to-date, a total of 6,000 cardiovascular ADRs caused by ICIs (Ipilimumab, Nivolumab, Pembrolizumab, Cemiplimab, Atezolizumab, Avelumab and Durvalumab), and 500 ADRs by ACTs (Kymriah, Yescarta, Tecartus, Brevanzi and Abecma) have been reported. ICI therapies were predominantly associated with myocarditis (1098), cardiac failure (614), acute coronary syndrome (548) and pericarditis/pericardial effusion (516). ACT therapies were associated with tachyarrhythmia (263), cardiac arrest (44) and cardiorenal events (25). A propensity analysis demonstrated ICIs to be associated with autoimmunity-related ADRs, whereas ACTs were associated with acute cytokine release-related ADRs. Conclusions: Using a large-scale global WHO data platform, we have identified unique tendencies for cardiovascular ADRs resulting from non-selective (ICIs) and highly-selective (ACTs) immunotherapies for cancer: the former is associated with serious autoimmune effects, and the latter is associated with acute cytokine-release-related ADRs.