(535) Immune Checkpoint Inhibitor-Related Myasthenia Gravis: A Case Report

Introduction: Pembrolizumab is an immune checkpoint inhibitor (ICI) used in various neoplasms due to its immune activation effect secondary to PD-1 protein blockade. It has been shown to significantly improve disease-free survival in patients with renal cell carcinoma when used as an adjuvant therapy after surgery. Immune-related myasthenia gravis (IrMG) is a rare complication of checkpoint inhibitor therapy with only a 0.12-0.24% incidence rate but a fatality rate of 10.2-47%.

Description: A 69-year-old male with stage III renal cell carcinoma treated with right nephrectomy presented to the hospital with diplopia, dysphagia, ptosis, facial weakness, dysarthria, and dyspnea after 2nd cycle of pembrolizumab therapy. On admission, his vitals were stable except he had mild hypoxemia. His neurological exam showed intact reflexes and sensation to gross touch but had prominent oculo-bulbar and bilateral upper extremity weakness. CSF analysis showed mildly elevated protein levels. MRI brain did not show any significant abnormalities. During his hospitalization, he developed multiple episodes of brady-arrhythmia including first-degree AV block, bi-fascicular block, and Mobitz type I second-degree AV block requiring permanent pacemaker placement. But he also continued to have progressively worsening neuromuscular weakness with hypoxia and increasing oral secretions requiring intubation. His negative inspiratory force was -10. He was treated with a 5-day course of IVIG and then started on pyridostigmine. He was also initiated on a tapering regimen of prednisone with gradual improvement of his symptoms. Anti-AchR antibody titer came back positive confirming Sero-positive IrMG.

Discussion: Though rare, IrMG is a fatal complication of ICI therapy with rapidly progressive symptoms. Up to 45% of patients require mechanical ventilation. Up to 8% cases of IrMG have concurrent myocarditis which was shown to have worse clinical outcomes. Early initiation of IVIG therapy irrespective of symptom severity has shown improved outcomes as compared to steroids alone. This case highlights the need for higher awareness regarding adverse effects of immunotherapy given improved outcomes with early management. Successful resumption of ICI therapy is possible in some cases after oral corticosteroids treatment.