Abstract: PUB201
A Case of Immune Checkpoint Inhibitor-Induced Overlap Syndrome with Clinical Pearls for the Nephrologist
Session Information
Category: Onconephrology
- 1600 Onconephrology
Authors
- Hargous, Emily Rose, Medical University of South Carolina, Charleston, South Carolina, United States
- Hendrix, Curtis Anthony, Medical University of South Carolina, Charleston, South Carolina, United States
- Budisavljevic, Milos N., Medical University of South Carolina, Charleston, South Carolina, United States
Introduction
This case highlights a variant of immune checkpoint inhibitor-induced overlap syndrome, an overlap of three immune-related adverse events from immune checkpoint inhibitors (ICI) - myasthenia gravis, myositis, and myocarditis. There is currently no consensus guidance for management with lack of standardized diagnostic criteria making ongoing research, early recognition, and prompt treatment imperative.
Case Description
A 57 year old female with uterine serous adenocarcinoma and recent carboplatin/paclitaxel/dostarlimab treatment presented with shortness of breath, chest pain, and weakness. She was found to have concerns of myocarditis with elevated NT-PRO BNP to 3,450 pg/ml and troponin to 345 ng/L despite a normal echocardiogram and cardiac MRI. Her creatine kinase was elevated at 1,782 U/L and her myositis panel was positive for anti SS-A 52kD Ab IgG. She had weakness and myasthenia like features but negative MuSK and AChR antibodies. She ultimately required intubation for acute hypoxic respiratory failure due to worsening serial NIFs. She received treatment with high dose steroids and Abatacept followed by 1 session of plasma exchange (PLEX). However, her course was complicated by multiple infections limiting the use of PLEX and additional immunosuppressants. PLEX was later reinitiated due to autoimmune encephalitis with positive Nif Ifa and GAD65-B-R antibodies in the CSF. She ultimately improved following 5 PLEX sessions.
Discussion
Although most cases of ICI-related myocarditis occur in isolation, concurrent development of myositis and/or myasthenia gravis has been reported in up to 30-40% of cases. Further research is needed to define the diagnostic criteria as ICI-induced myositis tends to present broadly. Diagnosis is challenging given the lower positivity rates of anti-AChR antibodies and high seronegativity incidence. Emerging literature suggests high dose steroids alone may be insufficient and early escalation to combination immunosuppression with plasmapheresis, IVIG, or biologics is increasingly recommended. Plasmapheresis can both remove pathological antibodies from blood and promote rapid clearance of circulating drugs making early Nephrology engagement imperative. In our case, we could not confirm presence of myasthenia gravis, but there is speculation that autoimmune encephalitis may represent an unrecognized variant of ICI-induced overlap syndrome.