Cardiotoxicity of immune checkpoint inhibitors
Gilda Varricchi,Maria Rosaria Galdiero,Giancarlo Marone,Gjada Criscuolo,Maria Triassi,Domenico Bonaduce,Gianni Marone,Carlo G. Tocchetti +7 more
- Vol. 2, Iss: 4
TLDR
The mechanisms of the most prominent checkpoint inhibitors are described, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 and PD-L1 (eg, atezolizumab).Abstract:
Cardiac toxicity after conventional antineoplastic drugs (eg, anthracyclines) has historically been a relevant issue. In addition, targeted therapies and biological molecules can also induce cardiotoxicity. Immune checkpoint inhibitors are a novel class of anticancer drugs, distinct from targeted or tumour type-specific therapies. Cancer immunotherapy with immune checkpoint blockers (ie, monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligand (PD-L1)) has revolutionised the management of a wide variety of malignancies endowed with poor prognosis. These inhibitors unleash antitumour immunity, mediate cancer regression and improve the survival in a percentage of patients with different types of malignancies, but can also produce a wide spectrum of immune-related adverse events. Interestingly, PD-1 and PD-L1 are expressed in rodent and human cardiomyocytes, and early animal studies have demonstrated that CTLA-4 and PD-1 deletion can cause autoimmune myocarditis. Cardiac toxicity has largely been underestimated in recent reviews of toxicity of checkpoint inhibitors, but during the last years several cases of myocarditis and fatal heart failure have been reported in patients treated with checkpoint inhibitors alone and in combination. Here we describe the mechanisms of the most prominent checkpoint inhibitors, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 (eg, nivolumab, pembrolizumab) and PD-L1 (eg, atezolizumab). We also discuss what is known and what needs to be done about cardiotoxicity of checkpoint inhibitors in patients with cancer. Severe cardiovascular effects associated with checkpoint blockade introduce important issues for oncologists, cardiologists and immunologists.read more
Citations
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Journal ArticleDOI
Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.
Filipe Martins,Filipe Martins,Latifyan Sofiya,Gerasimos P. Sykiotis,Faiza Lamine,Michel H. Maillard,Montserrat Fraga,Keyvan Shabafrouz,Camillo Ribi,Anne Cairoli,Yan Guex-Crosier,Thierry Kuntzer,Olivier Michielin,Solange Peters,Georges Coukos,Georges Coukos,François Spertini,John A. Thompson,Michel Obeid,Michel Obeid +19 more
TL;DR: The epidemiology, treatment and management of the various immune-related adverse events that can occur in patients receiving immune-checkpoint inhibitors are described.
Journal ArticleDOI
CD8+ cytotoxic T lymphocytes in cancer immunotherapy: A review.
TL;DR: CD8 + T cell priming is directed essentially as a corroboration work between cells of innate immunity including dendritic cells (DCs) and natural killer (NK) cells with CD4 + T cells in adoptive immunity for making durable and efficient antitumor immune responses.
Journal ArticleDOI
Immune checkpoint inhibitors and cardiovascular toxicity.
TL;DR: The epidemiology of immune checkpoint inhibitor-mediated cardiotoxic effects, as well as their clinical presentation, subtypes, risk factors, pathophysiology, and clinical management, are discussed, including the introduction of a new surveillance strategy.
Journal ArticleDOI
Association Between Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque.
Zsofia D. Drobni,Zsofia D. Drobni,Raza M. Alvi,Jana Taron,Amna Zafar,Sean P. Murphy,Paula K. Rambarat,Rayma C. Mosarla,Charlotte E. Lee,Daniel A. Zlotoff,Vineet K. Raghu,Sarah Hartmann,Hannah K Gilman,Jingyi Gong,Leyre Zubiri,Ryan J. Sullivan,Kerry L. Reynolds,Thomas Mayrhofer,Lili Zhang,Udo Hoffmann,Tomas G. Neilan +20 more
TL;DR: Cardiovascular events were higher after initiation of ICIs, potentially mediated by accelerated progression of atherosclerosis and increased atherosclerotic plaque progression was attenuated with concomitant use of statins or corticosteroids.
Journal ArticleDOI
Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T)
Raza M. Alvi,Matthew J. Frigault,Michael G. Fradley,Michael D. Jain,Syed S. Mahmood,Magid Awadalla,Dae Hyun Lee,Daniel A. Zlotoff,Lili Zhang,Zsofia D. Drobni,Malek Z.O. Hassan,Emmanuel Bassily,Isaac Rhea,Roohi Ismail-Khan,Connor P. Mulligan,Dahlia Banerji,Aleksandr Lazaryan,Bijal D. Shah,Adam Rokicki,Noopur Raje,Julio C. Chavez,Jeremy S. Abramson,Frederick L. Locke,Tomas G. Neilan +23 more
TL;DR: There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab administration was associated with a lower rate of CV events.
References
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Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies
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Journal ArticleDOI
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