Neuromuscular Immune-related Adverse Events of Checkpoint Inhibitors. A Case Series at a Third-level Hospital in Argentina
Rodrigo Sanjinez1, Rocio Marquez2, Agustina Moroni5, Lucia Belen Varela4, Mariela Bettini1, Facundo Silveira1, Pablo Sosa6, Carolina Azcona4, Marcelo Rugiero Rodriguez3
1Adult Neurology, 2adult neurology, 3Neurology, Hospital Italiano de Buenos Aires, 4Hospital Italiano de Buenos Aires, 5Italian Hospital of Buenos Aires, 6Adult Neurology, hospital Italiano de Buenos Aires
Objective:
To Describe a case series of neuromuscular adverse events in oncology patients on immune checkpoint inhibitor treatment.
Background:
Immune checkpoint inhibitors (ICI’s) are an effective cancer immunotherapy, especially in advanced oncologic disease. Among the numerous adverse events reported, those that affect the neuromuscular system (PNS-irAEs), such as Myasthenia gravis (MG), Inflammatory Myopathies (IM), and neuropathies, are highly related to morbidity and mortality rates.
Design/Methods:
Patients receiving ICI’s treatment who presented with neuromuscular syndromes were included from December 2017 to August 2023.
Results:

Nine patients were identified, 8 were males. The median age was 76 years (62-79). Among the oncologic diseases, metastatic melanoma was the most frequent (33%). The ICI’s received included pembrolizumab (n=6, 66%), nivolumab (n=2, 22%), and durvalumab (n=1, 12%). The PNS-irAEs included the debut of MG associated with MI (n=6, 66%), MG (n=1, 12%), and necrotizing myositis (n=2, 22%). Six of these patients also had myocarditis (3 cases of MG, MI, and Myocarditis overlap syndrome).

The median number of ICI’s cycles received was 1.7 (range 1-2). The median number of days after the first dose until PNS-irAEs was 28 (16-60). All patients discontinued the ICI’s. Treatment included corticosteroids (n=9), intravenous immunoglobulin (n=8), plasma exchange (n=1), and Rituximab (n=1). 8 patients required an intensive care unit stay, with a median stay of 20 days. 5 patients showed positive response to treatment, while the remaining patients did not survive.


Conclusions:
In this series, the most common PNS-irAEs were MG and MI, although rare, these events can be potentially fatal. Due to the widespread use of ICI’s, physicians should remain aware to enable prompt recognition and management of PNS-irAEs to improve the prognosis.
10.1212/WNL.0000000000206339