Immune Checkpoint Inhibition-Related Myasthenia-Myositis-Myocarditis Responsive to Complement Blockade

Neurol Neuroimmunol Neuroinflamm. 2023 Oct 26;11(1):e200177. doi: 10.1212/NXI.0000000000200177. Print 2024 Jan.

Abstract

Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but come with immune-related adverse events (irAEs) that provide a novel challenge for treating physicians. Neuromuscular irAEs, including myositis, myasthenia gravis (MG), and demyelinating polyradiculoneuropathy, lead to significant morbidity and mortality.

Methods: We present a case of severe myasthenia-myositis-myocarditis overlap in a patient receiving ICIs for breast cancer. Clinical findings were recorded.

Results: A 47-year-old woman developed tetraparesis, dysphagia, and muscle pain during ICI treatment. MG with a thymoma had been diagnosed earlier. Neuromuscular overlap irAEs with cardiac affection was confirmed, and ICI treatment was discontinued. Given a lack of clinical response to standard therapies, a muscle biopsy was performed demonstrating complement deposition. Eculizumab treatment led to rapid improvement in muscle strength and cardiac function.

Discussion: Neuromuscular irAEs are associated with a high in-hospital mortality, and specific treatment strategies remain an unmet need. Here, early muscle biopsy enabled targeted therapy after standard approaches failed, thereby highlighting the value of identifying a specific treatment target. To improve therapeutic outcomes, the development of patient-tailored strategies for neuromuscular irAEs requires further studies.

Publication types

  • Case Reports

MeSH terms

  • Female
  • Humans
  • Immune Checkpoint Inhibitors
  • Middle Aged
  • Muscle Weakness
  • Myasthenia Gravis* / chemically induced
  • Myasthenia Gravis* / drug therapy
  • Myocarditis*
  • Myositis* / chemically induced
  • Myositis* / drug therapy
  • Myositis* / pathology

Substances

  • Immune Checkpoint Inhibitors