Cardiovascular complications of immune checkpoint inhibitors for cancer . (30th August 2022)

• Record Type: Journal Article
• Authors: Thuny, Franck; Naidoo, Jarushka; Neilan, Tomas G
• Is Part Of: European heart journal. Volume 43:Number 42(2022)
• Page Start: 4458
• Page End: 4468
• Publication Date: 2022-08-30
• Subjects: Immune checkpoint inhibitors -- Myocarditis -- Atherosclerosis -- Cancer; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac456
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Over the last decade or so, there has been a paradigm shift in the oncologic care of patients with a range of solid tumour and haematologic malignancies, away from traditional cytotoxic chemotherapy and towards personalized cancer treatments, using both targeted therapy and immunotherapy. This shift has contributed to the remarkable and sustained increase in the number of cancer survivors and the longevity of patients with a cancer diagnosis. This review will focus on the cardiovascular effects of immune checkpoint inhibitors and will present a background on immune checkpoint inhibition for cancer, the epidemiology, potential mechanisms, the potential insights into cardiovascular biology, and a diagnostic and therapeutic approach to potential cases. Our understanding of the cardiovascular effects of immune checkpoint inhibitors needs to improve. However, the evolution necessarily needs to be rapid. Initial observations noted that immune checkpoint inhibitor therapy can lead to a fulminant myocarditis. Recent reports have expanded the effect of immune checkpoint inhibitor therapy on the cardiovascular system to include an increase in cardiac dysfunction without myocarditis, arrhythmias, venous thromboembolic disease, accelerated atherosclerosis, and atherosclerosis-related cardiovascular events. The association between immune checkpoint inhibitor therapy and an increase in these cardiovascular events is not only limited to events occurring within the first few weeks after starting therapy but can also include events that occur months to years after therapy. The latter observation is especially of relevance in those treated with adjuvant or neoadjuvant therapy. There needs to be a shift from recognition of an increase in cardiovascular events to currently approved immune checkpoint inhibitor therapies to understanding the mechanisms that lead to adverse cardiovascular effects, understanding who is at risk, and understanding what we can do about it. Graphical Abstract: Graphical Abstract Proposed eight-point-based management of patients with a suspicion for a cardiovascular immune-related adverse event. a Troponin testing may be positive if Troponin I or T is >99th percentile of the upper reference limit. Concomitant myositis may result in significant elevations of CK, CK isoforms, and even Troponin T. In patients with pre-therapeutic troponin elevation, a 50% increase of the level may be used as a cut-off, but no evidence currently supports this recommendation. b Haemodynamic instability, heart failure requiring non-invasive or invasive ventilation, complete or high-grade heart block, and/or significant ventricular arrhythmia. c Arrhythmias, conduction abnormalities, acute coronary syndromes, stroke, thromboembolic events, and heart failure should be managed urgently according to the international guidelines. d Endomyocardial biopsy should be performed especially in unstable patients who cannot undergo urgent CMR and in patients with uncertain diagnosis. e See Table 2 . f Defined as hemodynamic instability or electrical instability or increasing troponin or decreasing left ventricular ejection fraction. g There are no data to recommend a standardized initial treatment strategy for the intensification of immunosuppressive therapy. For now, case series and case reports have shown the potential efficacy of anti-thymocyte globulin, intravenous immunoglobulin, plasma exchange, mycophenolate mofetil, tacrolimus, tocilizumab, abatacept, alemtuzumab, and tofacitinib. The decision regarding optimal therapy must be multidisciplinary, involving specialists in immunology and organ rejection. Infliximab was also proposed but was not incorporated into the algorithm because of its contraindication in acute heart failure. i Troponin elevation without cardiovascular signs/symptoms and negative investigations including EMB. ACS, acute coronary syndrome; CCU, coronary care unit; CK, creatine kinase; AchR, acetylcholine receptor antibodies; CMR, cardiac magnetic resonance; EMB, endomyocardial biopsy; irAE, immune-related adverse event; ICI, immune checkpoint inhibitor; NT-proBNP, N -terminal-pro-brain-natriuretic-peptide; SMB, skeletal muscle biopsy; TSH, thyroid-stimulating hormone; TTE, transthoracic echocardiography; TTS, takotsubo syndrome. Audio Abstract: