作者
Carlo G. Tocchetti,Dimitrios Farmakis,Yvonne Koop,María Sol Andrés,Liam S. Couch,Luigi Formisano,Fortunato Ciardiello,Fabrizio Pane,Lewis Au,Max Emmerich,Chris Plummer,Geeta Gulati,Sivatharshini Ramalingam,Daniela Cardinale,Christine Brezden‐Masley,Zaza Iakobishvili,Paaladinesh Thavendiranathan,Ciro Santoro,Jutta Bergler‐Klein,Kalliopi Keramida,Rudolf A. de Boer,Christoph Maack,Esther Lutgens,Tienush Rassaf,Michael G. Fradley,Javid Moslehi,En‐Hua Yang,Mihai Gheorghiade,Pietro Ameri,Jeroen J. Bax,Tomas G. Neilan,Joerg Herrmann,Amam Mbakwem,Mariana Mirabel,Hadi Skouri,Emilio Hirsch,Alain Cohen‐Solal,Aaron L. Sverdlov,Wiek H. van Gilst,Riccardo Asteggiano,Ana Barac,Bonnie Ky,Daniel J. Lenihan,Susan Dent,Petar Seferović,Andrew J.S. Coats,Marco Metra,Giuseppe Rosano,Sandra M. Swain,Teresa López‐Fernández,Alexander R. Lyon
摘要
ABSTRACT The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors ( ICIs ). The second class are cell‐based immune therapies including chimeric antigen receptor T lymphocyte ( CAR ‐T) cell therapies, natural killer ( NK ) cell therapies, and tumour infiltrating lymphocyte ( TIL ) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune‐related adverse events ( irAEs ), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune‐related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI ‐related myocarditis with cardiogenic shock to more common complications including less severe ICI ‐related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non‐inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI , CAR ‐T, NK, and TIL therapies . We also highlight gaps in the literature and where future research should focus.