Triple M overlap syndrome following pembrolizumab treatment: importance of multidisciplinary approach

The increasing use of immune checkpoint inhibitors in clinical practice is associated with a broad spectrum of immune-related adverse events, such as cardiac, rheumatological and neurological toxicities. Myocarditis is a life-threatening complication, and the concurrent development of myocarditis, myositis and/or myasthenia leads to difficulties in diagnosis, management and treatment. We describe a case presenting with this triple M overlap syndrome following pembrolizumab treatment. A man in his 80s with a background of chronic ischaemic heart disease, receiving pembrolizumab as first-line treatment for microsatellite instability locally advanced gastric cancer, presented after the second dose of treatment with muscle weakness, binocular diplopia and left ptosis. Elevated transaminases, creatine kinase and high-sensitivity troponin-T levels were revealed. ECG monitoring showed the development of an atrioventricular block, needing a temporary pacemaker. Immune-related myocarditis, myasthenia and myositis were suspected. High-dose corticosteroids were administered without clinical benefit, so an escalation of immunosuppression was needed, using infliximab and immunoglobulins.