Statin Intolerance, Anti‐HMGCR Antibodies, and Immune Checkpoint Inhibitor‐Associated Myositis: A “Two‐Hit” Autoimmune Toxicity or Clinical Predisposition?

• Published in: The oncologist (Dayton, Ohio) Ohio), 2020-08, Vol.25 (8), p.e1242-e1245
• Main Authors: von Itzstein, Mitchell S., Khan, Shaheen, Popat, Vinita, Lu, Rong, Khan, Saad A., Fattah, Farjana J., Park, Jason Y., Bermas, Bonnie L., Karp, David R., Ahmed, Murtaza, Saltarski, Jessica M., Gloria‐McCutchen, Yvonne, Xie, Yang, Li, Quan‐Zhen, Wakeland, Edward K., Gerber, David E.
• Format: Article
• Language: English
• Subjects: Brief Communications
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2019-0911

Immune‐related adverse events induced by immune checkpoint inhibitor (ICI) therapy may affect diverse organ systems, including skeletal and cardiac muscle. ICI‐associated myositis may result in substantial morbidity and occasional mortality. We present a case of a patient with advanced non‐small cell lung cancer who developed grade 4 myositis with concurrent myocarditis early after initiation of anti‐programmed death ligand 1 therapy (durvalumab). Autoantibody analysis revealed marked increases in anti‐3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase antibody levels that preceded clinical toxicity, and further increased during toxicity. Notably, the patient had a history of intolerable statin myopathy, which had resolved clinically after statin discontinuation and prior to ICI initiation. This case demonstrates a potential association between statin exposure, autoantibodies, and ICI‐associated myositis. This article presents the case of a patient with advanced non‐small cell lung cancer treated with PD‐L1 checkpoint blockade who developed grade 4 myositis. This case report describes the first known case of ICI‐induced myositis associated with anti‐HMGCR antibodies, a key enzyme in cholesterol biosynthesis.