A Case Report of Possible Pembrolizumab-Induced Myasthenia Gravis from an Italian University Hospital: A Fatal Case Report

• Published in: Drug safety Vol. 45; no. 10; pp. 1245 - 1246
• Main Authors: Pivato, L, Brunoro, R, Mengato, D, Alberti, A, Bello, L, Venturini, F
• Format: Journal Article
• Language: English
• Published: Auckland Springer Nature B.V 01.10.2022
• Subjects: Adverse events; Apoptosis; Case reports; Chemotherapy; Clear cell-type renal cell carcinoma; Drug therapy; Dysphagia; Emergency medical care; Emergency medical services; Health services; Immunoglobulins; Immunotherapy; Intravenous administration; Kidney cancer; Monoclonal antibodies; Myasthenia; Myasthenia gravis; Neuromuscular junctions; Patients; PD-1 protein; Pembrolizumab; Pharmacology; Pharmacovigilance; Plasmapheresis; Targeted cancer therapy
• ISSN: 0114-5916; 1179-1942

Introduction: Pembrolizumab is a monoclonal antibody, Programmed death-1 (PD-1) inhibitor, currently approved for the treatment of a wide range of malignancies. This immunotherapy has a favorable efficacy/safety profile even though it could be related to very serious and sometimes fatal adverse events [1]. In particular, pembrolizumab use has been associated with several life-threatening immune-related adverse events. Among them, Myasthenia Gravis (MG) induced by pembrolizumab was rarely reported previously in the medical literature [2]. Objective: To present a clinical case report concerning a patient with possible pembolizumab-induced MG treated at our university hospital. Methods: Starting from a report of an adverse drug reaction (ADR) received by our Local Responsible for Pharmacovigilance (LRPV) and included in the National Pharmacovigilance Network, we retrospectively collected information about the drug therapy taken by the patient and his clinical history. Results: A 74-years-old Caucasian man with a diagnosis of clear cell renal cell carcinoma (ccRCC) since 2012, with more recent finding of additional pancreatic and pulmonary localizations, entered the emergency room in September 2021 with a suspected MG and deep bulbar involvement. Since July 2021, the patient has been treated according to the standard of care (S°C) with intravenous pembrolizumab and axitinib. Just a month later, he complained of general malaise, fatigue and a sense of heaviness in the neck with drooping of the head. The symptoms have worsened in dysphagia associated with marked dysarthria, hypophonia, difficulty in raising the upper limbs and walking. Episodes of diplopia were also reported. The clinical scenario suggests the indication for urgent hospitalization for appropriate clinical investigations. From the first results, a picture compatible with MG emerged. Immediately, the patient underwent appropriate treatment (such as intravenous immunoglobulins and high-dose corticosteroid therapy) followed by five consecutive plasmapheresis sessions. Nevertheless, the general conditions have worsened and the patient expired after 12-day hospitalization. Conclusion: Pembrolizumab, as many other PD-1 inhibitors, can provide great benefit to patients but can also be associated with rare but serious adverse events. Although rare, cases of pembrolizumab-associated MG are increasing. Early recognition of symptoms and possible discontinuation of pembrolizumab are necessary to improve prognosis. Finally, any adverse effects reported by patients should be closely monitored and evaluated.