Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor–Related Cardiotoxicity

Escudier, Marion; Cautela, Jennifer; Malissen, Nausicaa; Ancédy, Yann; Orabona, Morgane; Pinto, Johan; Monestier, S.; Grob, Jean‐Jacques; Scemama, Ugo; Jacquier, Alexis; Lalevée, Nathalie; Barraud, Jérémie; Peyrol, Michaël; Laine, Marc; Bonello, Laurent; Paganelli, Franck; Cohen, Ariel; Barlési, Fabrice; Éderhy, Stéphane; Thuny, Franck

doi:10.1161/circulationaha.117.030571

Cited by 425 publications

(444 citation statements)

References 5 publications

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“…11 In a retrospective series of patients with ICI-induced cardiotoxicity, complete reversibility of left ventricular dysfunction was observed in 8 of 12 patients who received corticosteroids compared with 1 of 6 patients who did not. 96 Furthermore, in the retrospective and prospective multicenter registry of patients with ICI-induced myocarditis, higher starting doses of steroids were associated with lower serum troponin and lower rates of major adverse cardiac events. 94 Therefore, guidelines recommend initial methylprednisolone pulse dosing (1 g/day for 3-5 days).…”

Section: Cardiovascular Toxicitymentioning

confidence: 98%

A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune‐modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.

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Section: Cardiovascular Toxicitymentioning

confidence: 98%

A review of cancer immunotherapy toxicity

Kennedy

Salama

2020

CA A Cancer J Clinicians

988

699

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“…Among this number, 43% of deaths were linked to cardiac events and neurological complications 17 . Escudier et al showed that among patients who developed cardiotoxicity, 1/3 of deaths were caused by a cardiological problem 18 . Cardiac mortality is significantly more common in patients with conduction disorders and those treated with combined immunotherapy 18 .…”

Section: Cardiotoxicity In Clinical Practicementioning

confidence: 99%

“…Escudier et al showed that among patients who developed cardiotoxicity, 1/3 of deaths were caused by a cardiological problem 18 . Cardiac mortality is significantly more common in patients with conduction disorders and those treated with combined immunotherapy 18 . An association of fatal cardiac complications with anti‐CTLA‐4 and anti‐PD‐1/PD‐L1 has also been demonstrated.…”

Section: Cardiotoxicity In Clinical Practicementioning

confidence: 99%

Cardiotoxicity danger in immunotherapy

et al. 2020

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Immunotherapy based on immune checkpoint inhibitors (ICIs) is currently broadly used in the treatment of different types of cancer. The treatment targeting programmed cell death protein 1/programmed death-ligand 1 axis is already approved by Food and Drug Administration for numerous cancers.These kinds of therapy brought spectacular results in the treatment of nonsmall cell lung cancer where systemic therapy was ineffective. However, a wide range of applied therapies based on ICIs in the clinic have led to unexpected side effects, such as severe cardiotoxicity. It needs to be underlined that the molecular mechanism of myocarditis in response to ICIs is still not fully understood. Lack of sufficient knowledge, especially concerning the kind of risk factors increasing probability of myocarditis, poses currently a large clinical problem. Continuous cardiac monitoring of patients who undergo ICI treatment presents another problem as it is cost-ineffective for the healthcare system. Herein, we highlight the risks of use of anticancer therapy based on ICIs. We also stress that detailed monitoring of any event of cardiotoxicity following ICIs treatment should be carefully investigated and registered to give a global overview of the frequency of myocarditis occurrence. Moreover, we propose that the extension of molecular and systemic knowledge of etiology of myocarditis as a side effect, including the role of protein kinases, will be highly beneficial for the medical field. Last but not least, better understanding of mechanisms of cardiotoxicity induction will improve the safety of cancer patients and will help clinicians in prediction of unexpected side effect occurrence.

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“…Celý vyšetřovací algoritmus začíná elektrokardiogramem a echokardiografií, dvěma bazálními neinvazivními vyšetřovacími metodami. Pro myokarditidu mohou svědčit nespecifické změny vlny T, objevit se mohou i nové poruchy převodu, arytmie či elevace ST úseku, u kterých je pak nutné vyloučit akutní koronární syndrom [7]. Změny elektrokardiografie lze pozorovat u 40 % pacientů a až 70 % pacientů má sníženou ejekční frakci levé komory [6,8].…”

Section: Klinický Obraz a Dia Gnostikaunclassified

Immunotherapy-Associated Myocarditis

Spisarová¹

2020

Klin Onkol

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SouhrnCheckpoint inhibitory významně ovlivňují křehkou rovnováhu mezi aktivací a inhibicí T lymfocytů v celém organizmu. Právě tímto mechanizmem se mohou nejen uplatnit v léčbě celé řady nádorových onemocnění, ale také mohou usnadňovat autoimunitní reakce. Léky této skupiny mohou způsobit exacerbaci již přítomného autoimunitního onemocnění nebo jej spustit u pacienta, který dosud autoimunitním onemocněním vůbec netrpěl. Protilátky cílené na kontrolní body cyklu imunitní odpovědi, ať už anti-CTLA4, či anti-PD-1/ PD-L1, jsou obecně dobře tolerovanými léky, avšak je nutno mít na paměti jejich širokou škálu nežádoucích účinků spojených s mechanizmem jejich působení, mezi které se mimo jiné řadí i kardiotoxické nežádoucí účinky. Lymfocytární myokarditida je považována za hlavní mechanizmus, který je následně zodpovědný za různé spektrum kardiovaskulárních nežádoucích účinků -od asymptomatické elevace kardiomarkerů přes projevy srdečního selhání, arytmie až po kardiogenní šok. Mezi další nežádoucí účinky se řadí postižení perikardu či Tako-tsubo kardiomyopatie. Klíčová slovaimunoterapie -checkpoint inhibitory -nežádoucí účinky -kardiotoxicita -myokarditida

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Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor–Related Cardiotoxicity

Cited by 425 publications

References 5 publications

A review of cancer immunotherapy toxicity

A review of cancer immunotherapy toxicity

Cardiotoxicity danger in immunotherapy

Immunotherapy-Associated Myocarditis

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