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Cardiovascular toxicities of immune therapies for cancer – a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology
European Journal of Heart Failure ( IF 16.9 ) Pub Date : 2024-08-01 , DOI: 10.1002/ejhf.3340
Carlo Gabriele Tocchetti 1 , Dimitrios Farmakis 2 , Yvonne Koop 3, 4 , Maria Sol Andres 5 , Liam S Couch 6 , Luigi Formisano 7 , Fortunato Ciardiello 8 , Fabrizio Pane 7 , Lewis Au 9, 10, 11 , Max Emmerich 12, 13, 14 , Chris Plummer 15 , Geeta Gulati 16, 17, 18 , Sivatharshini Ramalingam 5, 19 , Daniela Cardinale 20 , Christine Brezden-Masley 21 , Zaza Iakobishvili 22, 23, 24 , Paaladinesh Thavendiranathan 25 , Ciro Santoro 26 , Jutta Bergler-Klein 27 , Kalliopi Keramida 28 , Rudolf A de Boer 29 , Christoph Maack 30, 31 , Esther Lutgens 32 , Tienush Rassaf 33 , Michael G Fradley 34 , Javid Moslehi 35 , Eric H Yang 36 , Gilles De Keulenaer 37 , Pietro Ameri 38, 39 , Jeroen Bax 40 , Tomas G Neilan 41 , Joerg Herrmann 42 , Amam C Mbakwem 43 , Mariana Mirabel 44 , Hadi Skouri 45 , Emilio Hirsch 46 , Alain Cohen-Solal 47 , Aaron L Sverdlov 48, 49 , Peter van der Meer 50 , Riccardo Asteggiano 51, 52 , Ana Barac 53 , Bonnie Ky 54 , Daniel Lenihan 55 , Susan Dent 56 , Petar Seferovic 57 , Andrew J S Coats 58 , Marco Metra 59 , Giuseppe Rosano 60, 61 , Thomas Suter 62 , Teresa Lopez-Fernandez 63, 64 , Alexander R Lyon 65
Affiliation  

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.

中文翻译:


癌症免疫疗法的心血管毒性 – ESC 心力衰竭协会 (HFA) 和 ESC 心脏肿瘤学委员会的科学声明



在过去十年中,免疫疗法的出现彻底改变了实体癌和血液系统癌症的治疗。激活免疫系统以靶向癌细胞的许可疗法大致可分为两类。第一类是抑制免疫检查点信号传导的抗体,称为免疫检查点抑制剂 (ICI)。第二类是基于细胞的免疫疗法,包括嵌合抗原受体 T 淋巴细胞 (CAR-T) 细胞疗法、自然杀伤 (NK) 细胞疗法和肿瘤浸润淋巴细胞 (TIL) 疗法。所有这些治疗的临床疗效通常大于风险,但免疫相关不良事件 (irAE) 的发生率很高,这些不良事件的时间通常是不可预测的,临床后遗症从轻度(例如皮疹)到严重甚至致命(例如心肌炎、细胞因子释放综合征)和可逆到永久性(例如内分泌病)。支持irAE病理学的机制因不同的irAE并发症和综合征而异,反映了观察到的广泛临床表型和不同个体免疫反应的可变性,总体上知之甚少。免疫相关的心血管毒性已经出现,我们的理解已经从最初的关注罕见但致命的 ICI 相关心肌炎伴心源性休克发展到更常见的并发症,包括不太严重的 ICI 相关心肌炎、心包炎、心律失常,包括传导系统疾病和心脏传导阻滞、非炎症性心力衰竭、章鱼壶综合征和冠状动脉疾病。在这份关于癌症免疫疗法的心血管毒性的科学声明中,我们总结了 ICI、CAR-T、NK 和 TIL 疗法的病理生理学、流行病学、诊断和管理。 我们还强调了文献中的空白以及未来研究的重点。
更新日期:2024-08-01
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