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Sensorineural Hearing Loss After Adoptive Cell Immunotherapy for Melanoma Using MART-1 Specific T Cells

A Case Report and Its Pathophysiology

Duinkerken, Charlotte W.*; Rohaan, Maartje W.; de Weger, Vincent A.; Lohuis, Peter J. F. M.*,§; Latenstein, Merel N.*; Theunissen, Eleonoor A. R.||; Balm, Alfons J. M.*,§; Dreschler, Wouter A.; Haanen, John B. A. G.; Zuur, Charlotte L.*,§

doi: 10.1097/MAO.0000000000002332
SENSORINEURAL HEARING LOSS AND TINNITUS
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Objective: To illustrate a case of sensorineural hearing loss (SNHL) after immunotherapy based on T cell receptor (TCR) gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma.

Patient: We present a 59-year-old woman with profound subacute bilateral SNHL including unilateral deafness after immunotherapy based on TCR gene therapy using modified T cells recognizing melanoma antigen recognized by T cells 1 for disseminated melanoma. Ten days after treatment, the patient developed hearing loss of 57 dB hearing loss air conduction at pure-tone average 0.5–1–2–4 kHz in the right ear, and >100 dB hearing loss air conduction at pure-tone average 0.5–1–2–4 in the left ear. The right ear recovered partially, while the left ear remained deaf, despite oral prednisolone (1.0 mg/kg) and salvage treatment with three transtympanic injections of 0.5 ml dexamethasone (4.0 mg/ml).

Conclusion: Based on our presented case and a vast amount of literature there is circumstantial evidence that TCR gene therapy for melanoma targets the perivascular macrophage-like melanocytes in the stria vascularis, resulting in SNHL. We suggest that SNHL after TCR gene therapy may be caused by a disruption of the blood–labyrinth–barrier and the endolymphatic potential and/or a sterile inflammation of the stria vascularis. In severe cases like our subject, we posit that endolymphatic hydrops or hair cell loss may cause irreversible and asymmetrical deafness. Steroid prophylaxis via transtympanic application is debatable.

*Department of Head and Neck Oncology and Surgery

Department of Medical Oncology

Division of Pharmacology, the Netherlands Cancer Institute, Amsterdam, the Netherlands

§Department of Maxillofacial Surgery

||Department of Otorhinolaryngology

Department of Audiology, Amsterdam University Medical Center, Amsterdam, the Netherlands

Address correspondence and reprint requests to Charlotte W. Duinkerken, M.D., Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; E-mail: c.duinkerken@nki.nl

The authors disclose no conflicts of interest.

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