Triple M Syndrome After Immune Checkpoint Inhibition: A Rare and Life-Threatening Triad of Myocarditis, Myositis, and Myasthenia Gravis

Triple M syndrome is a well-known complication of pembrolizumab and other immune checkpoint inhibition (ICI) therapy that entails three components, namely, myocarditis, myositis, and myasthenia gravis, which can present independently or as part of an overlap syndrome. We present the case of an 80-year-old patient with stage 3C non-small cell lung carcinoma who complained of bulbar and ocular symptoms after the second cycle of pembrolizumab. Based on the integrated clinical picture and comprehensive biochemical markers, a provisional diagnosis of triple M syndrome was established. The patient was initiated on immunomodulatory therapy consisting of intravenous methylprednisolone and intravenous immunoglobulin (IVIG), administered over a five-day course. Despite first-line immunotherapy, the patient's condition deteriorated within four days of hospital admission. Plasmapheresis was considered but deemed unfeasible due to being too unstable to transfer to the tertiary centre to provide this. Given the lack of therapeutic response, the multidisciplinary team, in agreement with the patient's family, elected to transition the goals of care toward palliation and symptom-focused management. This case report, together with previous reports, underscores the critical importance of maintaining a high index of suspicion for triple M syndrome and initiating prompt intervention in patients receiving ICI therapy. Early identification and timely management are essential for optimizing clinical outcomes and are pivotal in preventing mortality.