Pembrolizumab-induced myasthenia crisis, myocarditis, myositis, and hepatitis

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Report Posters 13 SESSION TYPE: Case Report Posters PRESENTED ON: 10/10/2023 09:40 am - 10:25 am INTRODUCTION: Pembrolizumab is an immune checkpoint inhibitor and anti-PD-1 monoclonal antibody approved to treat 18 malignancies. Monotherapy pembrolizumab can cause fatigue, musculoskeletal pain, rash, pyrexia, and a constellation of gastrointestinal effects in over 20% of patients. The development of myasthenia syndrome/myasthenia gravis is recognized as a rare side effect which can lead to increased mortality from respiratory failure. Here we depict a case of pembrolizumab induced myasthenia crisis, myocarditis, myositis, and hepatitis in the ensuing weeks after pembrolizumab initiation. CASE PRESENTATION: A 59-year-old female with a history of renal cell carcinoma was started on pembrolizumab and axitinib. Three weeks later she presented with ptosis, diplopia, chest discomfort, and dyspnea. Labs revealed high sensitivity troponin 8,656, CK 1063, AST 115, and ALT 122. EKG showed non-specific ST-T wave changes while echocardiography displayed global LV systolic dysfunction. Neurology, hematology/oncology, and cardiology services were consulted. Given a high suspicion for an immunotherapy induced cause, the patient was started on 1g methylprednisolone daily. Myasthenia gravis antibody panel revealed a positive titer for anti-acetylcholinesterase receptor (anti-AChr) at 0.13. Her negative inspiratory force and forced vital capacity were closely monitored, and the patient was able to avoid mechanical ventilation with steroid therapy. Plasmapheresis and IV immunoglobulin were not required, and further therapy with pembrolizumab was aborted. DISCUSSION: When myasthenia is suspected with pembrolizumab, testing should be performed for antibodies, specifically anti-AChr (positive in 66% of cases). There is considerable overlap between myasthenia and myocarditis with the same antibodies involved. Negative inspiratory force and vital capacity should be monitored closely to evaluate for respiratory failure. The foundation of management is pulse dose, weight-based corticosteroids. Adjunctive therapies to consider include pyridostigmine, plasmapheresis, and IV immune globulin. The decision to pursue these options is dependent on the severity of the patient's symptoms. Hepatitis is usually asymptomatic and resolves with steroids. Regardless of the adverse effect, the recommendation is to discontinue the offending agent. CONCLUSIONS: With increasing use of immune checkpoint inhibitors as immunotherapy, it is essential for intensivists to be mindful of the adverse effects, especially the atypical presentation of myasthenia gravis. Prompt diagnosis, close monitoring in an ICU setting, and rapid institution of treatment is imperative. REFERENCE #1: Brahmer JR, Abu-Sbeih H, Ascierto PA, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events. J Immunother Cancer. 2021;9(6):e002435. doi:10.1136/jitc-2021-002435 REFERENCE #2: Dugena O, Zheng C, Taylor J, Wong A. Pembrolizumab-induced Myasthenia Gravis: Literature Review of Ocular Manifestations and a Refractory Case. J Immunother. 2022;45(6):267-273. doi:10.1097/CJI.0000000000000422 REFERENCE #3: Huang YT, Chen YP, Lin WC, Su WC, Sun YT. Immune Checkpoint Inhibitor-Induced Myasthenia Gravis. Front Neurol. 2020;11:634. Published 2020 Jul 16. doi:10.3389/fneur.2020.00634 DISCLOSURES: No relevant relationships by Craig Cookman No relevant relationships by Mark Malesker No relevant relationships by Bryce Schutte No relevant relationships by Abhisekh Sinha Ray