Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ipilimumab is a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) that is approved by the US Food and Drug Administration for the treatment of unresectable or metastatic melanoma. Ipilimumab is known to cause immune-mediated adverse reactions because of the resultant increase in T-cell activity. To date, there are no published reports of ipilimumab-related heart failure, although a recently published report describes a case of transient cardiomyopathy associated with its use. We report the case of a 60-year-old man who developed left ventricular dysfunction with an asymptomatic reduction in ejection fraction from 55%-60% at baseline to 40%-45% 4 months after completing a second course of treatment with ipilimumab for metastatic melanoma. Ipilimumab was not restarted, and the patient was initiated on lisinopril and carvedilol. Repeat echocardiograms 3 and 5 months later revealed ejection fractions of 40%-45% and 55%-60%, respectively.
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PMID:Left Ventricular Dysfunction After Treatment With Ipilimumab for Metastatic Melanoma. 2688 8

Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Over the last years, cancer immunotherapies haverevolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis. Immune checkpoint inhibitors are at the forefront of immunotherapy: the two most prominent are the targeting of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA- 4) and of programmed cell death 1 (PD-1) and its ligand PD-L1. Ipilimumab (anti-CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed. Inhibitors of CTLA-4 and PD-1/PD-L1 pathway can unleash anti-tumor immunity and mediate cancer regressions. Although CTLA-4 inhibitors and PD-1 and PD-L1 blocking agents are frequently associated with a wide spectrum of immune-related adverse events, cardiac toxicity has been underestimated. However, early animal studies have demonstrated that after CTLA-4 inhibition and PD-1 deletion autoimmune myocarditis can occur. Moreover, PD-1 and PD-L1 can be expressed in rodent and human cardiomyocytes. During the last years several cases of fatal heart failure have been documented in melanoma patients treated with checkpoint inhibitors. The recent experience with cardiovascular toxic effects associated with checkpoint inhibitors introduces important concepts biologically and clinically relevant for future oncology trials and clinical practice.
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PMID:Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue. 2840 86