[Pubmed] Rechallenge of immune checkpoint inhibitors in a case with adverse events inducing myasthenia gravis

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J Immunother Cancer. 2022 Nov;10(11):e005970. doi: 10.1136/jitc-2022-005970.

ABSTRACT

The mechanism(s) of immune checkpoint inhibitor (ICI)-induced myasthenia gravis (MG), an immune-related adverse event (irAE) that is fatal and limits subsequent ICI use, remain unexplored. Here, through comparative genomic analysis, we identified a pathogenic p.S467C germline variant in SLC22A5 in a thymoma case with ICI-induced MG, which was found to be associated with fatty acid oxidation through its regulation on L-carnitine levels. Remarkably, ICI rechallenge with L-carnitine pretreatment led to durable response without MG-related symptoms. Thus, we provide the first clinical evidence of genetic test-directed irAE management, which integrates individualized ICI treatment into the evolving paradigm of cancer management.

PMID:36450378 | DOI:10.1136/jitc-2022-005970


Source: https://pubmed.ncbi.nlm.nih.gov/3645037 ... 3&v=2.17.8