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J Immunother Cancer. 2015 Apr 21;3:11. doi: 10.1186/s40425-015-0057-1. eCollection 2015.

Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma.

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Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.
Department of Biomedicine, Cancer Immunology Laboratory, University of Basel, Basel, Switzerland.
Division of Cardiology, University Hospital Basel, Basel, Switzerland.
Institute of Pathology, University Hospital Basel, Basel, Switzerland.
Contributed equally


Antibodies that stimulate the immune system by targeting inhibitory T cell receptors were successfully introduced into oncological practice and are capable to overcome tumor-induced immune evasion. In particular, targeting of the inhibitory receptors CTLA-4 and PD-1 or its ligand PD-L1 have been shown to be beneficial for patients with melanoma, renal cell cancer, non-small cell lung cancer and a growing list of other cancers with impressive response rates. Here, we report a severe, potentially life-threatening side effect of anti-PD-1 immunotherapy with pembrolizumab, which has not been previously described in the literature. A 73-year-old woman with metastatic uveal melanoma treated with pembrolizumab in third line developed severe heart failure due to pembrolizumab-mediated autoimmune myocarditis. Echocardiographic studies revealed a severely impaired left ventricular function with dyssynchrony. All tests for cardiotropic viruses were negative and histological analysis of a myocardial biopsy showed lymphocytic infiltration with a predominance of CD8 positive cells and a reduction of FOXP3 positive regulatory T cells. After initiation of corticosteroids and guideline-conform heart failure therapy, the symptoms rapidly improved and the left ventricular function recovered. While autoimmune myocarditis is a documented side effect of other checkpoint inhibitors, as for example ipilimumab and in one case with anti-PD-L1 antibody, it is not described for anti-PD-1-antibodies like pembrolizumab or nivolumab. As the FDA recently approved both pembrolizumab and nivolumab for melanoma progressing after anti-CTLA-4 treatment with ipilimumab, more patients will soon receive anti-PD-1 therapy. Thus, it is important to be aware of such rare, but severe immune-related adverse events.


Anti-tumor T cell response; Antibody; Autoimmunity; Immunotherapy; Melanoma; Myocarditis; Nivolumab; PD-1 blockade; Pembrolizumab

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