ICIs have revolutionized the treatment of metastatic cancers. By upregulating immune responses, ICIs may cause autoimmune complications, including myopathies.

To describe clinical features and outcome in patients with immune checkpoint inhibitor (ICI)-associated myopathies.

We retrospectively identified patients seen at our institution between 2015 and 2019 with ICI-associated myopathy diagnosed pathologically, electrophysiologically or by abnormal extraocular muscle MRI.

We identified 22 patients with ICI-associated myopathies [ICIs used: pembrolizumab (15), nivolumab (3), avelumab (1) and combined ipilimumab and nivolumab (3)]. Median age-at-onset was 68.5 years (range 27-86). Patients received 1-18 ICI doses (median 2) prior to symptom onset. Eleven patients (50%) developed ptosis and/or ophthalmoparesis at onset; six had subtle or no limb weakness. Three patients developed respiratory failure requiring intubation and 4 developed myocarditis. Nine underwent muscle biopsy which showed a necrotizing myopathy (NM) without inflammation. Five patients with predominant ocular symptoms had abnormal MRI of the extraocular muscles. The median creatine kinase (CK) level was 262 IU/L (range:109-598) in ocular predominant, 611 IU/L (range:23-5839) in generalized myopathy and 429 IU/L (range:26-2865) in biopsy-proven NM patients. Nine patients were tested for anti-HMGCR and anti-SRP antibodies and were seronegative. AChR antibodies were elevated in 3/16 patients without electrophysiological evidence of neuromuscular transmission defect. ICI were withheld in all patients, 20 received immunomodulatory/suppressive therapies. Six patients died from myopathy-related cardiorespiratory complications. Factors associated with mortality (p<0.05) included initial respiratory symptoms, intubation requirement, no immunomodulatory/suppressive therapy and lymphopenia. Compared to 40 ICI-naïve NM patients [Anti-HMGCR-seropositive (19); anti-SRP-seropositive (3)] diagnosed during the same period, biopsy-proven ICI-associated NM had significantly higher frequency of extra-ocular muscle involvement, myocarditis, respiratory failure, and lymphopenia, and lower CK levels (p <0.05).

ICI-associated myopathies can present with generalized weakness associated with severe cardiorespiratory involvement or extra-ocular predominant phenotype. Normal or mildly elevated CK values do not exclude the diagnosis.