(977) PLEX to the Rescue in Triple M Syndrome's Myasthenic Crisis

Introduction: Immune checkpoint inhibitors (ICI) are approved for treatment of a variety of malignancies but can cause 3 life-threatening immune related adverse events: myocarditis, myositis, and myasthenia gravis (MG), referred to as triple M syndrome. Although high dose steroids are the standard treatment for myocarditis and myositis, steroids can exacerbate MG and treatment with IV immunoglobulin (IVIG) and plasmapheresis (PLEX) may be indicated. We present a case of ICI induced MG with progressive muscular weakness despite steroids and IVIG, that was successfully managed with PLEX.

Description: A 73-year-old man with high grade bladder cancer undergoing treatment with pembrolizumab presented to the hospital with worsening dyspnea and diffuse muscle weakness 3 weeks after the first cycle of immunotherapy. Neurological exam showed right eye ptosis, and reduced strength of cervical and distal muscles. Laboratory workup showed elevated creatine phosphokinase of 947 U/L and positive acetylcholine receptor antibody. ECG showed normal sinus rhythm with a new right bundle branch block. Transthoracic echocardiogram and brain natriuretic peptide were normal. Chest CT was negative for thymoma. MRI of the spine showed no spinal disease. The negative inspiratory force was -49 cm H20, and the forced vital capacity was 2.88 liters. Electromyography showed decreased conduction velocity in the right median motor and sensory nerves, and the right ulnar sensory nerve. High dose IV methylprednisolone was initiated (1 gram daily for 3 days, followed by a prednisone taper) with no significant effect. On day 9, he was started on IVIG (for a total of 5 doses of 0.4 gram per kg) for progressive bulbar weakness, double vision, dysphonia, and increased work of breathing. He was admitted to the ICU for management of hypercapnic respiratory failure and placed on noninvasive positive pressure ventilation. Urgent PLEX was initiated on ICU day 1 with remarkable improvement in the strength of cervical and distal muscles.

Discussion: ICI-induced MG is rare and often overlaps with myocarditis and myositis. Early diagnosis and discontinuation of the ICI, and treatment with steroids and IVIG are the mainstays. In cases of persistent myasthenia crisis, early use of PLEX is crucial to prevent rapid progression and mortality.