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

• Published in: Journal for immunotherapy of cancer 2015-04, Vol.3 (1), p.11-11, Article 11
• Main Authors: Läubli, Heinz, Balmelli, Cathrin, Bossard, Matthias, Pfister, Otmar, Glatz, Kathrin, Zippelius, Alfred
• Format: Article
• Language: English
• Subjects: Antibodies; Autoimmunity; Biopsy; Cancer; Cancer therapies; Cardiomyopathy; Cardiovascular agents; Care and treatment; Case Report; Clinical trials; Complications and side effects; Development and progression; Disease; Drug approval; Drug therapy; Dyspnea; Electrocardiography; Heart; Heart failure; Immunotherapy; Kidney cancer; Lung cancer, Non-small cell; Lymphocytes; Melanoma; Metastasis; Mutation; Myocarditis; Patients; Radiation therapy; Response rates; T cells; Viral antibodies
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-015-0057-1

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.