Audiovestibular Dysfunction Associated with Adoptive Cell Therapy for Melanoma

Abstract

Objective: 1) Understand the audiologic and vestibular toxicity associated with Adoptive Cell Therapy (ACT) for melanoma, which utilizes T-cells engineered with receptors to target the tumor-associated antigens MART-1 and gp100. 2) Investigate the use of intratympanic steroid injections in the treatment of audiovestibular dysfunction associated with ACT for melanoma.

Method: Retrospective review of 33 patients with metastatic melanoma nonresponsive to conventional therapy who underwent ACT with modified T-cells targeting MART-1 (n = 19) or gp100 (n = 14) from 2007 to 2008. All patients received serial audiometric testing. Vestibular testing was performed on patients with vestibular complaints. Patients with significant hearing loss received intratympanic steroid injections.

Results: Out of 33 patients, 16 had no hearing loss, 9 had mild hearing loss, and 8 had moderate hearing loss posttreatment. Ten patients received intratympanic steroid injections for mild (n = 3) or moderate (n = 7) hearing loss. Of those with mild hearing loss all but one recovered fully. Five of 8 patients with moderate hearing loss recovered to baseline hearing levels and 3 had partial recovery. There was vestibular dysfunction in 7 patients who underwent vestibular testing, one recovered fully, and the others showed partial recovery or no recovery. The number of modified T-cells infused for therapy correlated with the degree of audiovestibular deficit.

Conclusion: ACT targeting pigmented cell antigens is a novel therapy for melanoma that is associated with hearing loss and vestibular dysfunction. The presumed mechanism of autoimmune attack on normal melanocytes in the stria vascularis of the cochlea and vestibular organs demonstrates the importance of melanocytes in normal inner ear function.