Immune-Mediated Overlap Syndrome AfterAdjuvant Pembrolizumab in Melanoma: A CaseReport of Severe Multisystem Immune-RelatedAdverse Events

Abstract

Immunotherapy with immune checkpoint inhibitors (ICIs) has significantly improved survival in advanced and high-risk resected melanoma; however, it can induce multisystem immune-related adverse events (irAEs). ICI-induced myocarditis is rare, occurring in approximately 1% of cases, but it is potentially fatal, especially when it coexists with myositis and myasthenia gravis within the immune-mediated overlap syndrome. We report the case of a 50-year-old woman with stage IIIC dorsal epithelioid melanoma who underwent surgery and received adjuvant pembrolizumab,
presenting with eyelid ptosis, acute dyspnea, and tachyarrhythmia after the second cycle. Clinical, biochemical, and imaging evaluation confirmed an immune-mediated overlap syndrome with myocarditis, myositis, pneumonitis, and thyroiditis. The patient developed severe complications that required invasive mechanical ventilation and prolonged hospitalization in the intensive care unit (ICU) for five months, with progression to proximal and distal quadriplegia secondary to myositis. Treatment with high-dose methylprednisolone, followed by mycophenolate and plasmapheresis, achieved clinical  stabilization with normalization of cardiac biomarkers. This case highlights the importance of multidisciplinary management, early recognition, and immunosuppressive treatment to improve the prognosis in severe irAEs associated with ICIs.