review · European Journal of Heart Failure
Modern immunotherapies for cancer, including immune checkpoint inhibitors and cellular treatments such as chimeric antigen receptor T-cell therapies, have transformed oncology care. Although the benefits of these treatments generally outweigh their hazards, they frequently cause unpredictable immune-related adverse events ranging from mild skin reactions to life-threatening complications. Cardiovascular toxicities represent an important subset of these reactions. While clinical attention previously centred on rare, fatal myocarditis accompanied by cardiogenic shock, recognised problems now encompass milder myocarditis, pericarditis, heart failure, arrhythmias, conduction disorders, takotsubo syndrome, and coronary artery disease. The biological mechanisms driving these varied toxicities remain poorly understood. Addressing these clinical challenges requires consolidating current knowledge regarding the biological pathways, frequency, diagnosis, and clinical management of heart-related complications across distinct immunotherapy classes, alongside identifying critical gaps for ongoing clinical investigation.
Cancer immunotherapies save lives, but their tendency to trigger unintended heart damage poses a serious clinical dilemma. Clarifying the full spectrum of cardiovascular complications helps doctors identify risks earlier, tailor cardiac monitoring, and treat complications more safely. Improved recognition of these heart conditions ensures that patients undergoing cutting-edge cancer care can receive effective anti-tumour treatments without facing avoidable or unmanaged cardiovascular risks.
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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.
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DOI: 10.1002/ejhf.3340
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