Open AccessAudiovestibular Dysfunction Associated with Adoptive Cell Immunotherapy for Melanoma
Author(s) -
Seaman Bradley J.,
Guardiani Elizabeth A.,
Brewer Carmen C.,
Zalewski Christopher K.,
King Kelly A.,
Rudy Susan,
Van Waes Carter,
Morgan Richard A.,
Dudley Mark E.,
Yang James C.,
Rosenberg Steven A.,
Kim H. Jeffrey
Publication year - 2012
Publication title -
otolaryngology–head and neck surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.232
H-Index - 121
eISSN - 1097-6817
pISSN - 0194-5998
DOI - 10.1177/0194599812448356
Subject(s) - medicine , hearing loss , vestibular system , inner ear , melanoma , audiology , cancer research , anatomy
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 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.