Antibody-positive paraneoplastic neurological syndromes associated with immune checkpoint inhibitors: a systematic review

Background and objectives This study aimed to describe the clinical and prognostic characteristics of antibody-positive paraneoplastic neurological syndrome (PNS) associated with immune checkpoint inhibitors (ICIs). Methods We conducted a systematic review of relevant publications in PubMed and Embase from inception to December 2023. Patients with positive anti-neuronal antibodies who had a definite, probable, or possible diagnosis of PNS based on the 2021 PNS-Care Score criteria were included. Results A total of 76 records with 108 antibody-positive ICI-PNS patients were included in this systematic review. According to the updated 2021 criteria, 60.2% of patients were classified as definite PNS, 29.6% as probable PNS, and 10.2% as possible PNS. The median age was 66 years (range: 26-82), and 56.5% of patients were male. The most frequently associated tumors included lung cancer, melanoma, and Merkel cell carcinoma, and 72.2% of patients developed neurological symptoms within 6 months after ICIs treatment. The most common clinical phenotypes were limbic encephalitis (35.2%), rapidly progressive cerebellar syndrome (19.4%), and Lambert-Eaton myasthenic syndrome (13.0%), while the most common autoantibodies were anti-Hu (34.3%), anti-Ma2 (16.7%), and anti-P/Q VGCC (14.8%) antibodies. CSF inflammation was observed in 63.0% patients, predominantly lymphocytic. Corticosteroids were the mainstay of immunotherapy (90.9%), followed by intravenous immunoglobulin (IVIG) and plasma exchange. Outcome information was reported for 103 patients. The median follow-up was 4 months (IQR: 2, 10), and 56.3% of patients showed improvement, while 37.0% of patients died at the last follow-up. Patients with anti-Hu or anti-Ma2 antibodies had a higher proportion of deterioration and mortality (P < 0.05). Conclusion Limbic encephalitis and anti-Hu antibody are relatively common in antibody-positive ICI-PNS, and most patients present with CSF inflammation. Discontinuation of ICIs and corticosteroids are the main treatments. High-risk antibodies may be a risk factor for an unfavorable prognosis, particularly anti-Hu and anti-Ma2 antibodies.