Incidence and outcomes of neuromuscular immune-related adverse events in head and neck cancer patients treated with checkpoint inhibitors

Abstract

Abstract Immune checkpoint inhibitors (ICIs) are a transformative therapy for many cancers, including head and neck cancer (HNC). However, their unique mechanism can trigger immune-related adverse events. Rare but significant are immune-related neuromuscular complications, impacting quality of life and prognosis. Using the TriNetX Global Health Research Network, 17,112 HNC patients treated with ICIs were analyzed for neuromuscular complications (inflammatory myopathies, myocarditis, myasthenia gravis, and neuropathies) identified via ICD-10 codes. Frequencies, timing, and survival probabilities were compared between patients with and without complications. The vast majority of the cohort received anti-PD-1 therapy. Neuromuscular complications occurred in 2.09% of patients (355/17,112), with 437 total diagnoses indicating multiple complications per patient. Inflammatory myopathies were most common (54.23%), followed by myocarditis (27.92%), neuropathy (9.38%), and myasthenia gravis (8.47%). Patients with Myasthenia gravis complications were older (76 vs. 69 years), while neuropathy was more frequent in men, and inflammatory myopathies skewed toward women. Complications typically emerged within the first few months of treatment, though inflammatory myopathies also developed after 12 months. Survival analysis showed no significant difference between patients with and without complications, except for myocarditis, which was associated with worse survival. With our very large cohort of patients treated with immune checkpoint inhibitors (ICIs), we can demonstrate that neuromuscular complications of ICI therapy are rare but clinically significant. Cardiac involvement, particularly myocarditis, carries the worst prognosis. Prompt recognition and multidisciplinary management by oncologists and neurologists are essential to optimize outcomes in affected patients.