<p>Cardiac toxicity of immune-checkpoint inhibitors: a clinical case of nivolumab-induced myocarditis and review of the evidence and new challenges</p>

Abstract

Immune checkpoint inhibitors have revolutionized cancer treatment due to their undeniable efficacy, but a range of new adverse events (AE) has emerged. In particular, cardiac toxicity is a potentially fatal AE, and introduces new challenges regarding its underlying molecular mechanisms of occurrence, optimal treatment and follow up, and prevention. We present a clinical case of a patient with advanced kidney cancer treated with nivolumab as a third line treatment. After four cycles, the patient developed nonspecific symptoms and was hospitalized, identifying a set of clinical, analytical and electrocardiographic alterations compatible with myocarditis. Despite the intensive support, the patient died and a necropsy study was performed. We present a detailed description of the clinical case including the pathological and molecular findings, and we conduct a review of the available evidence related to immune-mediated cardiac toxicity to offer some new highlights in the management of this AE.

NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells

“…To date, the mechanisms and key players of ipilimumab-induced myocardial injuries are not completely understood [ 69 ]. Immune cells uptake and infiltration in heart tissues were always seen in human histological studies with high amounts of CD4+/CD8+ T lymphocytes and CD68+ cells [ 70 ]; this interaction involves some chemokines like Interleukin 1, 6, and 8 and chemokines that increase the granzyme B-mediated cytotoxicity driving cardiac injury [ 71 ]. Treatment with ipilmumab and other ICIs increase the cancer cell recognition of lymphocytes and their release of cytotoxic degranulation markers perforin and granzyme B [ 72 ].…”

Immune Checkpoint Inhibitor-Associated Cardiotoxicity: Current Understanding on Its Mechanism, Diagnosis and Management

“…(b* = 7) (Ederhy et al, 2018; Frigeri et al, 2018; Matson et al, 2018; Agrawal et al, 2019; Charles et al, 2019; Fazel and Jedlowski, 2019; Khoury et al, 2019). (c* = 8) (Johnson et al, 2016a; Arangalage et al, 2017; Chen et al, 2018; Martin Huertas et al, 2019; Salem et al, 2019). (d* = 7) (Arangalage et al, 2017; Monge et al, 2018; Yamaguchi et al, 2018; Agrawal et al, 2019; Martin Huertas et al, 2019; Salem et al, 2019; So et al, 2019).…”

Development and clinical applications of cancer immunotherapy against PD-1 signaling pathway

“…Myocarditis, an inflammatory AE, is the most common cardiovascular toxicity associated with ICIs [65]. Patients who receive a combination of nivolumab and ipilimumab compared with those who receive nivolumab alone have a higher risk for myocarditis [66, 67]. Presentation of myocarditis could involve elevated serum cardiac biomarkers such as cardiac troponin and creatine kinase-muscle/brain [68].…”

“…The diagnoses and treatment of myocarditis is extremely important when administering ICIs. Treatment of myocarditis includes use of steroids with other classic heart failure management [67]. Anti-thymocyte globulin, an immunosuppressive treatment, has been reported as an effective drug against myocarditis.…”