Beyond the Expected: Rare Immune-Related Neuromuscular Toxicities of Checkpoint Inhibitors—A Real-World Experience

Abstract Immune checkpoint inhibitors (ICIs) are increasingly used across malignancies, but rare immune-related neuromuscular toxicities can be missed early and may be life-threatening, particularly when associated with myocarditis. This was a retrospective observational case series conducted at HCG Aastha Cancer Centre, Ahmedabad, India. All consecutive adult patients (≥18 years) treated with standard-dose ICI (alone or in combination with chemotherapy or other agents) from January 2024 to September 2025 were included. Patients with pre-existing neuromuscular disorders were excluded. Neuromuscular adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Diagnosis of neuromuscular toxicities was based on clinical symptoms and laboratory parameters: creatine phosphokinase for myositis, and anti-acetylcholine receptor and anti-muscle-specific kinase antibodies for myasthenia gravis. Patients were followed up for at least 6 months after ICI initiation. The study was approved by the institutional ethics committee (HCG Multispecialty Ethics Committee). Among 135 ICI-treated patients, 5 patients (3.7%) developed immune-related neuromuscular toxicities. The commonest symptom was muscle weakness (4 of 5 cases), followed by dysphonia (3 of 5 cases). One case of hepatocellular carcinoma developed severe bulbar muscle weakness following atezolizumab with bevacizumab. The second case with metastatic malignant melanoma on pembrolizumab developed an immune-related myositis–myasthenia–myocarditis overlap syndrome. Three other cases developed immune-related myasthenia gravis, one of whom also had pneumonitis. All the cases initially improved with high-dose steroids followed by prolonged oral steroids. Notably, biochemical markers (creatinine phosphokinase and myasthenia autoantibodies) were normal in most cases, underscoring diagnostic difficulty. Immune-related neuromuscular junction disorders and myopathies are uncommon but clinically important ICI toxicities that can present subtly and may be fatal when myocarditis coexists. Early recognition (even with normal biomarkers), prompt ICI interruption, and timely corticosteroids are critical to reduce morbidity and prevent progression to a fatal outcome.