title: Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma.
abstract: 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.
authors.affiliation: Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.|Department of Biomedicine, Cancer Immunology Laboratory, University of Basel, Basel, Switzerland.
authors.forename: Heinz
authors.initials: H
authors.lastname: Läubli
authors.affiliation: Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Balmelli
authors.affiliation: Division of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bossard
authors.affiliation: Division of Cardiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Otmar
authors.initials: O
authors.lastname: Pfister
authors.affiliation: Institute of Pathology, University Hospital Basel, Basel, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Glatz
authors.affiliation: Division of Medical Oncology, University Hospital Basel, Basel, Switzerland.|Department of Biomedicine, Cancer Immunology Laboratory, University of Basel, Basel, Switzerland.
authors.forename: Alfred
authors.initials: A
authors.lastname: Zippelius
keywords: Anti-tumor T cell response; Antibody; Autoimmunity; Immunotherapy; Melanoma; Myocarditis; Nivolumab; PD-1 blockade; Pembrolizumab