Pharmacovigilating cardiotoxicity of immune checkpoint inhibitors.

Abstract

Immune checkpoint inhibitors (ICIs) have greatly ameliorated clinical outcomes for several tumours and are now a cornerstone in antineoplastic treatments. Fighting cancer with antitumoural immune responses is not a completely novel concept, but the first attempts were not successful, because cancer cells can take advantage of inhibitory pathways mediated by CTLA-4, PD-1, and PD-L1 (all of which decrease the antineoplastic activity of T cells) to escape T cell-mediated anticancer immune responses. ICIs, such as monoclonal antibodies directed against CTLA-4, PD-1, and PD-L1, introduced in the past 10 years, however, have revolutionised anticancer strategies. Unfortunately, these drugs are also associated with some risk of cardiotoxicity, since blockade of the CTLA-4 and PD-1 axes can cause autoimmune myocarditis and dilated cardiomyopathy, as reviewed by our group 1 Varricchi G Galdiero MR Tocchetti CG Cardiac toxicity of immune checkpoint inhibitors: cardio-oncology meets immunology. Circulation. 2017; 136: 1989-1992 Crossref PubMed Scopus (71) Google Scholar and others, suggesting that these molecules can modulate autoimmunity. Mechanisms of ICI-associated myocarditis have not been clearly elucidated, but experimental studies have shown that deletion of PD-L1, and treatment with PD-L1-inhibiting molecules, can cause lethal myocarditis. Increased expression of PD-1 and PD-L1 has been reported on cardiomyocytes from rat hearts that underwent ischaemia reperfusion. 1 Varricchi G Galdiero MR Tocchetti CG Cardiac toxicity of immune checkpoint inhibitors: cardio-oncology meets immunology. Circulation. 2017; 136: 1989-1992 Crossref PubMed Scopus (71) Google Scholar Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance studyTreatment with ICIs can lead to severe and disabling inflammatory cardiovascular irAEs soon after commencement of therapy. In addition to life-threatening myocarditis, these toxicities include pericardial diseases and temporal arteritis with a risk of blindness. These events should be considered in patient care and in combination clinical trial designs (ie, combinations of different immunotherapies as well as immunotherapies and chemotherapy). Full-Text PDF