- 01/2021 melanoma of unknown primary (MUP)
- Initial stage: pTxNxM1c(0), IV (AJCC 2017), BRAF wild-type
- Metastases in lungs, liver, duodenum, gastric corpus, esophagus, and peritoneal carcinosis
- 02/2021 Combination immunotherapy with ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw, every three weeks (3 doses in total)
- 05/2021 - 04/2022 Immunotherapy with nivolumab 240 mg, every 2 weeks
After three doses of combination immunotherapy with ipilimumab 3 mg/kg bw and nivolumab 1 mg/kg bw, the patient developed visual impairment due to iritis that was treated topically with cortisone eye drops. Shortly thereafter, the patient reported dizziness, tinnitus, hearing impairment and balance disorder. An ENT examination showed caloric near-areflexia on both sides and a videooculographically pathological Halmagyi head impulse test. The ability to hear in the high-frequency range was limited in the audiogram. A bilateral vestibulopathy was diagnosed.
The patient received three bilateral intratympanic cortisone injections. The imbalance disorder improved significantly on the right and slightly on the left. The hearing ability in the high-frequency range improved. Subjectively, the patient also reported a significant improvement in gait and mobility stability.
After the patient’s general condition improved, we continued immunotherapy with nivolumab monotherapy. There was no exacerbation of the vestibulopathy, but the patient developed irColitis and also Uveitis and Vitiligo, suggesting Vogt-Koyanagi-Harada disease. With regard to the melanoma, the course of the disease remained stable.
Vestibulopathies are rare immune-mediated side effects and have been described with various immunotherapies (nivolumab, ipilimumab+nivolumab, ipilimumab and pembrolizumab). Both with and without therapy, patients often show little or no improvement in vestibular symptoms (Voskens et al., J Clin Oncol, 2012; Mendis et al. Eur J Canc, 2021; Lemasson et al., Eur J Canc, 2019; Koch et al., J Immuother, 2021; Stürmer et al., J Immunother, 2021). Intratympanical cortisone application is an alternative to systemic cortisone administration (Salt et al., Drug Discov Today, 2005). A correlation between the time from the onset of vestibulopathy to the start of therapy and the response is probable. Therefore, physicians should be aware of immune-mediated vestibulopathy and conduct a prompt ENT consultation in suspected cases.
