Severe immune checkpoint inhibitor-induced 3M syndrome: a case report

Immune checkpoint inhibitors (ICIs) have significantly improved survival rates in various advanced cancers, including cervical cancer. However, they can induce a range of immune-related adverse events (irAEs), with immune myocarditis being particularly dangerous, especially when combined with myositis and myasthenia gravis, forming the fatal 3M syndrome. Early symptoms are subtle, and delayed diagnosis and treatment often lead to severe consequences.

A 65-year-old female with stage FIGO stage IIIA cervical squamous cell carcinoma received one dose of anti-PD-1 monoclonal antibody (Enlarzumab) combined with chemoradiotherapy. Following initial disease stabilization, the patient developed early neuromuscular symptoms, including ptosis and facial weakness, on Day 21. By Day 25, she experienced sudden chest tightness and acute heart failure with new-onset atrial fibrillation and a decline in left ventricular ejection fraction from 57% to 40%. The concurrent elevation of cardiac biomarkers and creatine kinase, alongside neuromuscular involvement, confirmed the clinical diagnosis of ICI-induced 3M syndrome. Despite treatment with high-dose methylprednisolone, intravenous immunoglobulin (IVIG), and mycophenolate mofetil, the patient ultimately succumbed to progressive respiratory failure following the family's decision to decline further invasive respiratory support.

This case highlights the insidious onset and rapid progression of 3M syndrome, where neuromuscular symptoms often serve as overlooked precursors to myocarditis. Establishing a systematic approach involving proactive monitoring and immediate immunosuppressive treatment is essential to ensure the safety of immunotherapy.