Pharmacovigilating cardiotoxicity of immune checkpoint inhibitors
A partir des données de la base "Vigibase" de l'Organisation Mondiale de la Santé, cette étude rétrospective de pharmacovigilance analyse les toxicités cardiovasculaires induites par l'utilisation d'inhibiteurs de points de contrôle immunitaire pour traiter les patients atteints de cancer (31 321 événements indésirables identifiés)
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 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.
The Lancet Oncology , commentaire, 2017