Immune Checkpoint Inhibitor-Induced Myositis, Myocarditis, and Myasthenia Gravis Overlap Syndrome Following Nivolumab and Ipilimumab Combination Therapy in a 60-Year-Old Male With Metastatic Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs) are in widespread use for the treatment of some metastatic cancers. While generally well tolerated, these agents can elicit a spectrum of unintended effects due to indiscriminate immune system activation. These side effects may impact multiple organs simultaneously and can become life-threatening if not promptly addressed. One complication of ICI therapy presents with a combination of myasthenia gravis (MG) symptoms and inflammation of both skeletal and cardiac muscles. This report describes a 60-year-old male with metastatic clear cell renal cell carcinoma on nivolumab and ipilimumab combination therapy post-nephrectomy who presented to our emergency department with fatigue and shortness of breath. Although he reported swallowing difficulties on further enquiry, other classic neuromuscular deficits were absent. The MG composite score was 5, and vital signs were stable. Initial creatine kinase and troponin T were 6,376 U/L and 1,694 ng/L, respectively, and the electrocardiograph (ECG) and echocardiogram were unremarkable. Magnetic resonance imaging (MRI) of the thighs and myocardium showed changes consistent with myositis and myocarditis, respectively. Although an autoantibody screen for MG was requested and later came back negative, the initial diagnosis of MG was clinical. The patient was treated with IV methylprednisolone, IV immunoglobulin, pyridostigmine, and mycophenolate (MMF). The decision to pursue an aggressive multi-pronged immunosuppressive strategy was to minimise the risk of rapid deterioration due to inadequate treatment in a patient with a good functional baseline. Symptoms resolved by the third day of admission, and laboratory markers continued to improve steadily. He was successfully discharged on reduced-dose oral prednisolone and MMF with a plan for outpatient follow-up with twice weekly CK, troponins, and ECG. ICIs were permanently discontinued. Myositis, myocarditis, and MG (MMM) overlap syndrome is an uncommon but potentially fatal immune-related adverse event (irAE) associated with ICI therapy and requires urgent medical attention. Clinicians should maintain a high index of suspicion for rapid diagnosis, as symptoms can be vague. Patient education is also strongly recommended for awareness, as the incidence will likely rise with the expanding use of ICIs. Early and aggressive immunosuppression may help prevent morbidity and mortality.