Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data

Purpose Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. Methods We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were “hearing loss” OR “hearing impairment” OR “ototoxicity” OR “vestibular toxicity” OR “audiovestibular toxicity” AND “immune checkpoint inhibitor” OR “immunotherapy.” Results A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. Conclusion We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.