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

Abstract

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.

• Authors: Mitchell S von Itzstein, Shaheen Khan, Vinita Popat, Rong Lu, Saad A Khan, Farjana J Fattah, Jason Y Park, Bonnie L Bermas, David R Karp, Murtaza Ahmed, Jessica M Saltarski, Yvonne Gloria-McCutchen, Yang Xie, Quan-Zhen Li, Edward K Wakeland, David E Gerber
• Journal: The oncologist (Oncologist) Vol. 25 Issue 8 Pg. e1242-e1245 (08 2020) ISSN: 1549-490X [Electronic] England
• PMID: 32400023 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © AlphaMed Press 2020.

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Immune Checkpoint Inhibitors

Topics

• Carcinoma, Non-Small-Cell Lung
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (adverse effects)
• Immune Checkpoint Inhibitors
• Lung Neoplasms
• Myositis (chemically induced, drug therapy)