title: Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma.
abstract: OBJECTIVE
  To understand the audiologic and vestibular toxicities associated with adoptive cell immunotherapy (ACI) targeting pigment-pathway antigens on melanoma and to investigate the use of intratympanic steroid injections in the treatment of these toxicities.
  
  
  METHODS
  Prospective nonrandomized study.
  
  
  METHODS
  Tertiary clinical research center.
  
  
  METHODS
  Thirty-two patients with progressive metastatic melanoma who failed conventional therapy underwent ACI with T cells genetically modified to target MART-1 (n = 18) or gp100 (n = 14). All patients received serial audiometric testing. Vestibular testing was performed on patients with vestibular complaints. Patients with significant deficits received intratympanic steroid injections.
  
  
  RESULTS
  Of 32 patients, 15 had no hearing change, 9 had mild hearing loss, and 8 had moderate hearing loss following treatment. Ten patients received intratympanic steroid injections for mild (n = 2) or moderate (n = 7) hearing loss or for significant imbalance (n = 1). Of those with mild hearing loss (n = 9), all but 1 recovered to pretreatment hearing levels. Four of 8 patients with moderate hearing loss recovered to baseline hearing levels, and 4 had partial recovery. All 7 patients with posttreatment vestibular complaints had demonstrable vestibular dysfunction. Three of these patients demonstrated recovery to normal vestibular function. The number of modified T cells infused for therapy correlated with the degree of audiovestibular deficit.
  
  
  CONCLUSIONS
  Adoptive cell immunotherapy targeting pigment-pathway cell proteins, a novel therapy for melanoma, can induce hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the cochlear stria vascularis and in the vestibular organs demonstrates the importance of melanocytes in normal inner ear function.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Georgetown University Medical Center, Washington, DC 20007, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Seaman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Guardiani
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Zalewski
authors.forename: Kelly A
authors.initials: KA
authors.lastname: King
authors.forename: Susan
authors.initials: S
authors.lastname: Rudy
authors.forename: Carter
authors.initials: C
authors.lastname: Van Waes
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D056704:Adaptive Immunity; D000328:Adult; D001301:Audiometry, Pure-Tone; D016009:Chi-Square Distribution; D018450:Disease Progression; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D034381:Hearing Loss / Q000209:etiology*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects* / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use; D058965:MART-1 Antigen / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D011446:Prospective Studies; D014724:Vestibular Function Tests; D058951:gp100 Melanoma Antigen / Q000276:immunology
chemical_list: D005938:Glucocorticoids; D007376:Interleukin-2; D058965:MART-1 Antigen; D058951:gp100 Melanoma Antigen