(467) A Case of Avelumab-Associated Myasthenia Gravis, Myositis, and Multiorgan Failure

Introduction: The use of checkpoint inhibitors against programmed death ligand-1, and cytotoxic T-lymphocytes- associated protein-4 has become widespread in clinical practice1[1]. These immune checkpoint inhibitors such as Avelumab are associated with various adverse effects. We present a case of Avelumab associated Myasthenia Graves, myositis, and multi-organ failure

Description: A 68-year-old man with a history of high-grade Urothelial carcinoma of the renal pelvis was initiated on maintenance Avelumab 6 weeks after successful resection followed by adjunct chemotherapy. He presented to the hospital with dysphagia and bilateral ptosis for 4 days. On physical examination, dysarthria, bilateral bulbar weakness, dysphagia to solids and liquids, and generalized weakness were noted. Laboratory results revealed creatinine 1.7 mg/dl with eGFR of 43 ml/min/1.73 m2, elevated levels of aspartate aminotransferase 297 U/L, alanine transaminase 222 U/L, C-Reactive protein 1.4 mg/dl and erythrocyte sedimentation rate 35 mm/hr. Notably, creatinine kinase was increased at 8347 U/L. The patient's CSF analysis revealed elevated protein and glucose levels but molecular panel and cultures were unremarkable. Computed tomography of the chest revealed an eventration of the left hemidiaphragm and an echocardiogram revealed normal overall heart function. Magnetic resonance imaging of the brain showed no acute abnormalities. Autoimmune workup was positive for acetylcholinesterase receptor (AchR) binding antibody at 1.30 nmol/L and AchR blocking antibodies at 40%. Patient was transferred to intensive care unit due to worsening respiratory failure requiring positive pressure ventilation. A diagnosis of Avelumab-associated Myasthenia Gravis, myositis, and multi-organ failure was made. Patient was managed with intravenous immunoglobulin at a dose of 2 gm/kg divided over four days, Methylprednisolone 40 mg, and pyridostigmine resulting in clinical improvement. He was later transferred to a sister facility for plasmapheresis.

Discussion: Avelumab-associated myasthenia gravis, myositis, and multi-organ failure is a rare but life-threatening immune-mediated adverse event. Clinicians should suspect this diagnosis in patients presenting with dysphagia and bulbar symptoms, and initiate timely treatment to prevent fatal deterioration.