Dr Shah on Outcomes With Checkpoint Inhibition in Patients With Cancer and Pre-Existing Neurologic Autoimmune Disorders

"Although ICIs can be used safely [in this patient population], we still don't yet know [for] whom that is going to be the case. The likelihood of a relapse or severe worsening is relatively high [for patients with myasthenia gravis]. We have to be very careful when considering ICIs for these patients."

Shailee S. Shah, MD, a clinical assistant professor of Neurology (MS/Neuroimmunology) at Northwestern University Feinberg School of Medicine, shared findings from a retrospective cohort study assessing the exacerbation of pre-existing neurologic autoimmune disorders (NAIDs) in patients with cancer receiving immune checkpoint inhibitors (ICIs), as well as clinical outcomes with this therapy across conditions. 

The study included 135 patients with multiple sclerosis (n = 45), myasthenia gravis (n = 18), Guillain-Barré syndrome (n = 10), and Parkinson’s disease (n = 57), which served as the control cohort.

Results were published in JAMA Network Open, and showed that NAID exacerbations were most frequently observed in patients with myasthenia gravis, with 67% experiencing a relapse, Shah reported. Among these patients, 50% required hospitalization and 17% died, indicating a high risk of severe adverse effects. In contrast, the exacerbation rate in patients with multiple sclerosis was 18%, and there were no significant differences in cancer response rate, progression-free survival, or overall survival across the NAID subgroups.

Although patients with myasthenia gravis receiving active immunosuppressive therapy appeared less likely to experience exacerbations, the sample size was insufficient to determine statistical significance, Shah explained. Among those with exacerbations, half required hospitalization and immunosuppressive treatment, and 56% subsequently discontinued ICI therapy, she said. One patient who was rechallenged with an ICI after initiating immunosuppressive therapy tolerated it well, Shah noted. However, 2 patients died due to complications related to worsening myasthenia gravis.

These findings highlight the importance of careful risk–benefit assessment when considering ICIs for patients with pre-existing NAIDs, particularly myasthenia gravis, Shah asserted. Although durable oncologic responses were observed in many patients who continued ICI therapy, the potential for severe neurologic exacerbation must be weighed when determining treatment appropriateness in this high-risk subgroup, she concluded.