Outcomes in Patients With Immune Checkpoint Inhibitor-Related Myopathy and Prolonged Follow-Up.

Background and objectives: Myopathy is one of the most common neurologic immune-related adverse events (irAEs) reported after treatment with immune checkpoint inhibitor (ICI) cancer immunotherapies. Current knowledge on disease course relates to short-term outcomes, and long-term outcome data are lacking. The aim of this study was to evaluate the long-term outcomes of patients with ICI-related myopathy.

Methods: We reviewed Mayo Clinic patients diagnosed with ICI-related myopathy between 2013 and 2024 with at least 6 months of follow-up; we compared them with patients who died because of myopathy within 2 months from disease onset.

Results: Twenty-three patients were identified; the median follow-up duration was 13 months (range 6-76). The median age at presentation was 73 years (range 34-87), and 57% were male. The most common presentations were ocular involvement (78%, including oculomotor and ptosis), followed by proximal limb (74%), axial (61%), and bulbar (48%) weakness. Myocarditis was present in 35%. At disease nadir, 43% had an irAE grade >2. All patients were treated with corticosteroids; 61% received additional immunosuppressive/immunomodulatory treatment in the acute setting. The median treatment duration was 5 months (range 1-17). At the last follow-up, 87% of patients had a favorable outcome (irAE grade ≤2), yet residual symptoms/signs were common (48%). Gradual improvement was observed in most patients, even after immunosuppressive/immunomodulatory treatment was discontinued. The only patient with a truly refractory course had biopsy findings of nemaline rods. Compared with patients with long-term follow-up, patients who died within 2 months (N = 9) were more commonly men (57% vs 100%, p = 0.03) and more likely to have bulbar or axial involvement (p = 0.01 and p = 0.04, respectively).

Discussion: Approximately half of the patients with ICI-related myopathy and long-term follow-up had some residual symptoms/signs, despite good functional outcomes. Symptoms continue to improve over 12 months regardless of immunosuppressive/immunomodulatory treatment duration. Male sex and axial and bulbar symptoms/signs were all associated with a terminal disease course. A prolonged refractory disease course might suggest an atypical pathology.