Left Ventricular Dysfunction After Treatment With Ipilimumab for Metastatic Melanoma

Roth, Mary E; Muluneh, Benyam; Jensen, Brian C.; Madamanchi, Chaitanya; Lee, Carrie B.

doi:10.1097/mjt.0000000000000430

Cited by 52 publications

(28 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Non-inflammatory cardiovascular toxicities have been reported in individual cases. These include Takotsubo-like syndrome with both apical 6,25,26 and basal variants 27 ; asymptomatic non-inflammatory left-ventricular dysfunction 28 ; myocardial infarction 29 ; and coronary vasospasm. 30 Arrhythmias have also emerged as a sign of cardiotoxicity in patients receiving ICI.…”

Section: Overview Of Immune-related Adverse Events From Icismentioning

confidence: 99%

Cardiovascular toxicities associated with immune checkpoint inhibitors

Florido

Lipson

et al. 2019

Cardiovascular Research

359

300

View full text Add to dashboard Cite

Cardiovascular toxicities associated with immune checkpoint inhibitors (ICIs) have been reported in case series but have been underappreciated due to their recent emergence, difficulties in diagnosis and non-specific clinical manifestations. ICIs are antibodies that block negative regulators of the T cell immune response, including cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and PD-1 ligand (PD-L1). While ICIs have introduced a significant mortality benefit in several cancer types, the augmented immune response has led to a range of immune-related toxicities, including cardiovascular toxicity. ICI-associated myocarditis often presents with arrhythmias, may co-exist with myositis and myasthenia gravis, can be severe, and portends a poor prognosis. In addition, pericardial disease, vasculitis, including temporal arteritis, and non-inflammatory heart failure, have been recently described as immune-related toxicities from ICI. This narrative review describes the epidemiology, diagnosis, pathophysiology, and treatment of cardiovascular toxicities of ICI therapy, highlighting recent developments in the field in the past year. Keywords Cardio-oncology • Immune checkpoint inhibitors • Myocarditis • Vasculitis • Pericarditis • Cardiovascular toxicity This article is part of the Spotlight Issue on Cardio-oncology.

show abstract

Section: Overview Of Immune-related Adverse Events From Icismentioning

confidence: 99%

Cardiovascular toxicities associated with immune checkpoint inhibitors

Florido

Lipson

et al. 2019

Cardiovascular Research

359

300

View full text Add to dashboard Cite

show abstract

“… 87 114 115 117 In a multicentre retrospective study on 752 patients with melanoma treated with ipilimumab, one case of myocardial fibrosis was reported. 122 One case report revealed left ventricular dysfunction 123 and one case of Takotsubo cardiomyopathy after treatment with ipilimumab. 44 Interestingly, a late-onset ipilimumab-induced pericarditis was reported in a patient with melanoma.…”

Section: Cardiac Toxicity Of Checkpoint Inhibitors In Patients With Cmentioning

confidence: 99%

Cardiotoxicity of immune checkpoint inhibitors

et al. 2017

View full text Add to dashboard Cite

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.

show abstract

“…The incidences of cardiotoxicity have been reported in patients receiving checkpoint inhibitor therapy, including several fatal cases. In patients treated with ipilimumab and combination of ipilimumab and nivolumab, myocardial fibrosis, left ventricular dysfunction, Takotsubo cardiomyopathy and late-onset pericarditis were reported [10,[66][67][68][69]. There was one fatal case of myocardial infarction in a patient with NSCLC who received pembrolizumab [70].…”

Section: Preclinical Evidence Of Autoimmune Myocarditismentioning

confidence: 99%

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity

et al. 2018

View full text Add to dashboard Cite

The immune checkpoint molecules are emerged in the evolution to protect the host from self-attacks by activated T cells. However, cancer cells, as a strategy to survive and expand, can hijack these molecules and mechanisms to suppress T cell-mediated immune responses. Therefore, an idea of blocking the checkpoint molecules to enhance the anti-tumor activities of the host immune system has been developed and applied to the cancer therapy after discovery of the inhibitory T cell co-receptor, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and further enhanced on the identification of PD-1 and its ligands. Since 2010, several checkpoint inhibitors have been approved by FDA and many more are in clinical trials. In the treatment of advanced cancers, these inhibitors significantly increased response rates and survival benefits. However, accompanied with the striking results, immune-related adverse events (irAEs) that broadly occurred in many organs were observed and reported, some of which were fatal. Herein, we first review the recent progressions in the research of the immune checkpoint molecules and the application of their blocking antibodies in cancer treatment, and then discuss the cardiac toxicity induced by the therapy and the strategy to monitor, manage this adverse event when it occurs.

show abstract

Left Ventricular Dysfunction After Treatment With Ipilimumab for Metastatic Melanoma

Cited by 52 publications

References 9 publications

Cardiovascular toxicities associated with immune checkpoint inhibitors

Cardiovascular toxicities associated with immune checkpoint inhibitors

Cardiotoxicity of immune checkpoint inhibitors

Cancer immune checkpoint blockade therapy and its associated autoimmune cardiotoxicity

Contact Info

Product

Resources

About