Audiovestibular dysfunction associated with adoptive cell immunotherapy for melanoma

Bradley J. Seaman, Elizabeth A. Guardiani, Carmen C. Brewer, Christopher K. Zalewski, Kelly A. King, Susan Rudy, Carter Van Waes, Richard A. Morgan, Mark E. Dudley, James C. Yang, Steven A. Rosenberg, H. Jeffrey Kim

Research output: Contribution to journalArticlepeer-review

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. Study Design. Prospective nonrandomized study. Setting. 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. Conclusion. Adoptive cell immunotherapy targeting pigmentpathway 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.

Original languageEnglish (US)
Pages (from-to)744-749
Number of pages6
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume147
Issue number4
DOIs
StatePublished - Oct 1 2012

Keywords

  • adoptive cell immunotherapy
  • audiovestibular dysfunction
  • cochlea
  • hearing loss
  • melanocytes
  • melanoma
  • stria vascularis
  • vestibular dysfunction
  • vestibular organs

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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