RESUMO
OBJECTIVE: To ascertain trends in ototoxicity observed with monoclonal antibodies (mABs) and understand the impact they may have on hearing function. DATA SOURCES: PubMed, Embase, Scopus. REVIEW METHODS: A systematic review was performed following PRISMA guidelines. Data were reviewed for demographics, utilized mABs with respective indication and dosing, audiometric outcomes, and treatment for otologic effects. RESULTS: Of 757 studies reviewed, a total of 44 were included, encompassing 18,046 patients treated with mABs. Mean age of the sample was 57.8 years old. The search yielded 18 agents of ototoxicity, with reported symptoms of ototoxicity such as hearing loss, tinnitus, and/or aural fullness occurring in 1079 of total patients. Main agents causing ototoxicity were teprotumumab (n = 17/44 studies), nivolumab (n = 10/44), ipilimumab (n = 9/44), pembrolizumab (n = 5/44), and rituximab (n = 4/44). Thirty-one of 44 studies encompassing eight agents reported audiometric data for ototoxic agents, showing sensorineural hearing loss primarily in the high-frequency range. Only two articles performed ultrahigh-frequency audiograms. CONCLUSION: Monoclonal antibody usage is expanding, but the vast majority of studies lack substantial audiometric data. Where reported, study design and inclusion criteria vary greatly. Future studies would benefit from rigid inclusion of audiometric data, prospective study design, and consideration of formal ototoxicity screening. Otolaryngologists should be aware of the cochlear immune response and potential impact of this expanding medication class on hearing function. Laryngoscope, 2024.
RESUMO
OBJECTIVE: Hearing loss has been reported after administration of the monoclonal antibody teprotumumab. The purpose of this study was to review available evidence regarding the patterns of teprotumumab-related ototoxicity. DATA SOURCES: PubMed, EMBASE, and Cochrane Library. REVIEW METHODS: A systematic review was performed using standardized methodology. Studies were included if they included subjects who were prescribed teprotumumab. Exclusion criteria included non-English articles, abstracts, letters/commentaries, case reports, and reviews. Subjects without both pre- and posttreatment audiometric data were also excluded. Bias was assessed using the Mixed Methods Appraisal Tool. RESULTS: From an initial search of 76 articles, 7 studies reporting on 109 unique patients were included. Four studies were level 4 evidence, 1 study was level 3 evidence, and 2 studies were level 2 evidence. Mean age was 55 ± 14 years with a female predominance (64%). The most commonly reported symptoms were hearing loss (22%), followed by fullness (18%) and tinnitus (14%). In total, 41% of patients with available data met criteria for ototoxicity, all exhibiting shifts in the middle frequencies or higher. Fifteen (14%) patients underwent ultrahigh frequency audiometric testing and 8 (53%, 8/15) demonstrated shifts exclusively in this range. CONCLUSION: Ototoxicity may occur in patients treated with teprotumumab. Hearing loss occurs primarily in higher frequencies, and routine hearing screening with ultrahigh frequency testing may be warranted. The true incidence of ototoxicity with teprotumumab remains unknown, and more data is needed to elucidate underlying mechanisms and develop strategies to minimize risks.