A Fatal Case of Pembrolizumab Induced Myasthenia Crisis

Abstract Introduction: Myasthenia gravis is an immune mediated condition leading to inhibition of the neuromuscular junction causing muscle weakness. Myasthenic crisis refers to the severe state of myasthenia that involves respiratory muscle paralysis which leads to acute respiratory failure and can be life threatening. Myasthenia is a rare but serious consequence of the immune checkpoint inhibitor, pembrolizumab. Pembrolizumab is a PD-1 inhibitor approved for use in over a dozen malignancies. Description: An 87-year-old man with muscle invasive bladder cancer, was started on pembrolizumab and three weeks after first infusion he developed ptosis and generalized weakness. Further infusions were discontinued due to concern for immune checkpoint inhibitor toxicity and completed a four-week taper of oral prednisone. However, symptoms worsened with evidence of myopathy and transaminitis on labs and required hospitalization. On admission, he was dyspneic, wheelchair bound and underweight secondary to progressive dysphagia. MRI brain and spine were negative for leptomeningeal enhancement or metastasis. He received methylprednisolone and IVIG for five days with steady decrease in CK and transaminitis. Generalized weakness improved but dysphagia was unchanged. Serology was negative for myasthenia gravis, Lambert Eaton, paraneoplastic and Sjogren antibodies. No evidence of thymoma or metastasis on CT. Multidisciplinary evaluation concluded pembrolizumab related myasthenia as the leading diagnosis. Seronegative myasthenia could not be ruled out. Following a modest response to methylprednisolone and IVIG, symptoms returned and progressively worsened. Nasogastric tube feeding was required due to severe dysphagia. Negative inspiratory force was monitored throughout hospitalization which declined to less than -10 cmH20 when he was transferred to the intensive care unit for non-invasive positive pressure ventilation (NIPPV) and initiation of plasma exchange therapy. Patient declined intubation and NIPPV was continued despite worsening respiratory function. Unfortunately, his clinical status precipitously declined, and he expired prior to plasma exchange therapy initiation. Discussion: The expanding role of immune checkpoint inhibitors in cancer therapy necessitates critical care physicians be mindful of their severe and potentially life-threatening side effects. Known exposure to an immune checkpoint inhibitor should prompt a multidisciplinary approach with consideration for early escalation in therapy for severe or refractory symptoms.