title: Myasthenia triggered by immune checkpoint inhibitors: New case and literature review.
abstract: Immune checkpoint molecules are potent regulators of immunologic homeostasis that prevent the development of autoimmunity while maintaining self-tolerance. Inhibitors of immune checkpoint molecules are used as immunotherapy in the treatment of melanoma and different types of refractory cancer, and can trigger various autoimmune complications including myositis and myasthenia gravis. We describe a case of generalized myasthenia gravis induced by pembrolizumab and review 11 other cases. Five patients also had elevated serum CK levels ranging from 1200 to 8729 IU/L, and biopsy showed myositis in one. Severity was highly variable as symptoms normalized spontaneously in one patient, but three others developed myasthenic crisis (including two with fatal outcomes). Steroids have been recommended as a preferred treatment of autoimmune complications of immune-checkpoint inhibitors. Myasthenia gravis should be considered when weakness, diplopia or bulbar symptoms are seen after treatment with immune checkpoint inhibitors, and additional studies are needed to characterize association with hyperCKemia.
authors.affiliation: Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Natalia L
authors.initials: NL
authors.lastname: Gonzalez
authors.affiliation: Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Araya
authors.initials: A
authors.lastname: Puwanant
authors.affiliation: Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Angela
authors.initials: A
authors.lastname: Lu
authors.affiliation: Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15232, USA.
authors.forename: Stanley M
authors.initials: SM
authors.lastname: Marks
authors.affiliation: Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. Electronic address: zivkovics@upmc.edu.
authors.forename: Saša A
authors.initials: SA
authors.lastname: Živković
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D009157:Myasthenia Gravis / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C582435:pembrolizumab; D003402:Creatine Kinase
keywords: Cancer immunotherapy; HyperCKemia; Immune checkpoint inhibitor; Myasthenia gravis; Myositis