IMMUNE CHECKPOINT INHIBITOR-INDUCED MYASTHENIA GRAVIS: A RARE NEUROLOGIC COMPLICATION OF IMMUNOTHERAPY FOR UROTHELIAL CELL CANCER

Abstract

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Immune checkpoint inhibitors (ICIs) such as anti-programmed death 1 (anti-PD-1) antibodies are approved for the treatment of several malignancies. Anti-PD-1 agents function by blocking tumor cell and T-cell receptor-ligand binding, thereby permitting anti-tumor T-cell immune response. Unfortunately, ICIs have been associated with a variety of immune-related adverse events, including rare neurologic complications like myasthenia gravis (MG). CASE PRESENTATION: An 81-year-old Caucasian male with bladder cancer status post cystectomy presented with one week of progressive shortness of breath and weakness, transient right-sided facial droop, intermittent diplopia, and confusion 20 days after receiving adjuvant pembrolizumab. He was afebrile, hypertensive, tachycardic and hypoxic. Lungs were clear, and his neurologic exam was normal. CT angiogram showed bibasilar atelectasis. An arterial blood gas was consistent with acute hypercapnia. He was started on non-invasive ventilation (NIV) and empiric steroids (1.5 mg/kg), however, his respiratory failure progressed requiring intubation. MRI brain and cerebral spinal fluid studies were negative for acute pathology. An electromyogram was suggestive of MG prompting initiation of plasma exchange (PLEX) for presumed ICI-associated MG. Acetylcholine receptor antibodies returned positive days later. Despite treatment, he remained ventilator-dependent and opted to pursue palliative extubation. DISCUSSION: Myasthenia gravis (MG) is a disorder of the neuromuscular junction that can lead to fatigable ocular, bulbar, respiratory, and limb muscle weakness. Ptosis, dyspnea, and diplopia are common. A recent systematic review identified 63 cases of patients who developed MG symptoms after ICI initiation. Fifty-two of these patients had de novo disease; 11 experienced exacerbations of preexisting MG. The median time from first infusion to symptom onset was four weeks. Anti-acetylcholinesterase receptor or anti-striated muscle antibodies were positive in 66 percent of cases, and 60 percent of patients demonstrated electrodiagnostic evidence of MG or MG and myositis. This heterogeneity in presentation and diagnostic evaluation can lead to delays in diagnosis and treatment. ICI-associated MG can progress to respiratory failure in a median of seven days, and mortality ranges from 38 to 50 percent. Discontinuation of ICI and IVIG or PLEX are mainstays of therapy. CONCLUSIONS: ICI-associated MG is a rare complication of cancer immunotherapy. To our knowledge, this is only the second reported case of de novo ICI-associated MG in a patient with urothelial cell cancer. ICI-associated MG can occur early after ICI initiation and progress rapidly as highlighted by this case. MG should be considered in patients with new neurologic symptoms on ICI therapy. Reference #1: Safa H, Johnson DH, Rodgers TE, et al. Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature. Journal for ImmunoTherapy of Cancer. 2019;7:319. Reference #2: Kao JC, Liao B, Markovic SN, et al. Neurological complications associated with anti–programmed death 1 (PD-1) antibodies. JAMA Neurol. 2017;74(10):1216–1222. Reference #3: Becquart O, Lacotte J, Malissart P, et al. Myasthenia gravis induced by immune checkpoint inhibitors. J Immunother. 2019;42(8):309-312. DISCLOSURES: No relevant relationships by Christine Cook, source=Web Response No relevant relationships by Andrew Moore, source=Web Response No relevant relationships by Matthew Sharpe, source=Web Response