To report two cases of immune checkpoint inhibitor (ICI)-associated paraneoplastic disorders

ICIs are demonstrating tremendous efficacy for treatment of diverse solid tumor types resulting in a rapidly growing number of patients exposed to these therapies. As a result of their immune-activating mechanism of action, ICIs can trigger various immune-mediated toxicities, including neurological autoimmune syndromes.

Case Report

First case: a 71-year-old women with recurrent metastatic lung adenocarcinoma developed diplopia, ataxia, tremors, and urinary incontinence five months after initiating pembrolizumab-containing chemotherapy. Exam revealed rotary jerk and mixed upbeat nystagmus, right hypertropia and esotropia, and gait ataxia. MRI head and spine showed no abnormal signal enhancement. CSF analysis was notable for lymphocytic pleocytosis (WBC 10). Given concern for an ICI-induced immune-mediated process, her pembrolizumab was discontinued and she was treated with a prolonged steroid taper with gradual resolution of symptoms. After treatment initiation, CSF paraneoplastic panel demonstrated anti-Ri antibodies.

Second case: a 58-year-old male with chronic sensory neuropathy and recently diagnosed Merkel cell carcinoma developed a EMG-confirmed rapidly-progressive, severe sensory polyneuropathy after a single dose of pembrolizumab. Exam revealed decreased vibration and proprioception, pseudoathetotic movements in his upper and lower extremities, and a severely unsteady gait despite normal strength. Spine MRI revealed discrete dorsal column T2 hyperintensities and his serum was positive for anti-Hu antibodies. Work-up for his chronic neuropathy prior to his pembrolizumab initiation had demonstrated serum anti-Hu antibodies, though his slowly progressive course was thought not to represent anti-Hu neuropathy. Given concern for ICI-induced anti-Hu neuronopathy, his pembrolizumab therapy was discontinued.

We report two patients with paraneoplastic syndromes after starting ICI treatment. Research into biomarkers to predict risk of development or severity of paraneoplastic syndromes and other ICI-associated neurological toxicities is warranted. Additionally, there is also a need to establish efficacious treatment strategies for ICI-associated neurologic toxicities.