Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade

Abstract

Background: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment. Methods: A survey was distributed through the secure electronic data collection tool REDCap to neuroophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained. Results: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/ 31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven

Antibody-Mediated Autoimmune Diseases of the CNS: Challenges and Approaches to Diagnosis and Management

“…Neurological Autoimmunity Secondary to Immune Checkpoint Inhibitors ICI act by enhancing the immune response against cancers and are increasingly approved for treatment of different tumors. A common and unwanted effect of these drugs is autoimmunity, potentially directed against any organ (121)(122)(123)(124)(125). CNS autoimmunity may occur, generally within the first 3 months, and is accompanied by neural specific autoantibodies in approximately half of moderate-high severe cases.…”

Ocular Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Lung Cancer

“…Although ocular irAEs are infrequent based on the previous study, they can cause a deterioration of the quality of life and exert an influence on the compliance of patients. Lots of studies have reported the ocular adverse events secondary to ICIs (19,25,26,30,31,153,(164)(165)(166)(167)(168) and the grade of the adverse events had been published recently based on Common Terminology Criteria for Adverse Events. While no study had reported the ocular irAEs in lung cancer.…”

“…Moreover, it can be unilateral or bilateral. According to previous studies, ophthalmoplegia in lung cancer secondary to ICIs were accompanied by myasthenia gravis (MG) in all patients ( 25 , 34 – 39 , 46 , 47 , 49 – 51 , 55 – 57 , 60 , 64 , 69 – 76 , 79 , 81 ). Ptosis is the key manifestation of immune-related MG, and accounts for 75%–78.7% of ICI-induced MG (irMG) ( 93 – 96 ).…”

“…In this review, we summarized the reported ocular irAEs following ICIs in lung cancer by searching the PubMed database until April 2021 ( 25 , 29 , 33 – 86 ). The key words were a combination of ‘adverse events’, ‘lung’, and names of ICIs.…”

“…The prevalence of ICI-related pneumonitis is higher in NSCLC than in other tumor type, based on data from the Immuno-Cancer International Registry ( 23 , 24 ). In addition, lung cancer is reportedly one of the most common tumor with ICI-related ocular irAEs ( 25 ).…”