- 12/2019 cutaneous melanoma of the capillitium (Bresslow tumor thickness 1,2 mm)
- Initial stage: pT2aN0M0, IB (AJCC), BRAF wild-type, NRAS mutation, c-Kit wild-type
- 12/2020: disseminated pulmonary, hepatic and lymph node metastases
multiple sclerosis, no treatment due to stable disease
12/2020 – 02/2021 combined immunotherapy with ipilimumab and nivolumab (4 cycles)
Two weeks after initiation of the immunotherapy with ipilimumab and nivolumab the patient presented to the emergency room with nausea, fatigue and dizziness. Laboratory results showed hyponatriaemia as well as a low cortisol level (> 0,2 µg/dl) that could not be stimulated through ACTH. Hydrocortisone was initiated due to an immune-related hypophysitis. One week later the patient presented again to the emergency room due to progressive increase in muscle tone of the left leg and left arm as well as the loss of the ability to walk.
MRI scan of the brain did not show any new foci that could explain the acute deterioration. A lymphomonocytic pleocytosis with liquor-specific oligoclonal gammopathy was detected in liquor analysis. An acute exacerbation of the preexisting multiple sclerosis under immunotherapy was suspected. Therapy with methylprednisolone (1 g/d) was initiated for five days. Spasticity improved and the patient was able to walk short distances again.
Immunotherapy was interrupted due to this severe neurological immune-related adverse event. The symptoms remained stable even after discontinutation of the therapy with methylprednisolone. Staging showed regressive liver as well as pulmonary metastases in March 2021. Six months after the initiation of the immunotherapy high liver enzymes were detected (GOT: 1113 U/l,
GPT: 2154 U/l ). Due to immune-related hepatitis (CTCAE grade 4) a therapy with methylprednisolone was reinitiated, under which liver enzymes decreased.
Neurological irAEs are rare in less than 1% of patients under immunotherapy (Spain et al., Ann oncol. 2017), but might be underreported due to lack of recognition. There are few case reports about MS relapse under immunotherapy, with description of rapid neurological progression and even death. As in our example all patients suffered from other immune-related adverse events. (Garcia et al., Clin Transl Oncol. 2019). Most neurological adverse events show good response to steroids, especially if initiated promptly (Larkin et al., The Oncologist 2017). Prospective studies are neccessary to provide information about risk factors, clinical presentation, outcome and therapy optimization.
