Multiple nivolumab-induced CNS demyelination with spontaneous resolution in an asymptomatic metastatic melanoma patient

Abstract

BackgroundImmune checkpoint inhibitors (ICPis) have revolutionised the treatment of melanoma by significantly increasing survival rates and disease control. However, ICPis can have specific immune-related adverse events, including rare but severe neurological toxicity.Case presentationWe report a 44-year-old man diagnosed with stage IIIB melanoma who developed metastatic disease (pulmonary and brain metastases) and was treated with stereotactic radiosurgery and nivolumab immunotherapy. He developed asymptomatic multifocal diffuse white matter lesions consistent with active central nervous system demyelination seen on brain MRI. One month after cessation of the immunotherapy, spontaneous regression of the demyelinating lesions was observed, suggesting a nivolumab-related toxicity.ConclusionWe report the first case of a melanoma patient with an asymptomatic and spontaneously reversible central nervous system demyelination following nivolumab immunotherapy. This case highlights the need for better recognition of such atypical and rare neurological toxicities which could be mistaken for progressive brain metastases. Early recognition and appropriate management are crucial to reduce severity and duration of these toxicities, especially for patients with less favourable evolution.

Renal cell carcinoma with central nervous system demyelination caused by nivolumab

“…1 (Table 1). [4][5][6][7][8][9][10] Our report is the first case of CNS demyelination caused by nivolumab to treat RCC. All other reported patients were treated with steroids except for one patient with no symptoms who was relieved by only discontinuation of nivolumab.…”

“…To our knowledge, only eight cases of CNS demyelination owing to ICIs have been reported, including the present case (Table 1). 4–10 Our report is the first case of CNS demyelination caused by nivolumab to treat RCC. All other reported patients were treated with steroids except for one patient with no symptoms who was relieved by only discontinuation of nivolumab.…”

Central Nervous System Demyelination Associated With Immune Checkpoint Inhibitors: Review of the Literature

“…Of these cases, patients were classified as having the following syndromes: 7 with myelitis (19,(34)(35)(36)(37)(38)(39), four isolated optic neuritis (40)(41)(42)(43), one NMOSD (44), three had a relapse from a previously diagnosed MS (21,23,24), and two evolved from a radiologically isolated syndrome (RIS) to MS (22,45). Six patients had atypical demyelination (14,25,(46)(47)(48)(49). Class of ICI used was anti-PD-L1 in four patients, anti-CTLA-4 in eight, anti-PD-1 in eight, and a combination of anti-PD-1 and anti-CTLA-4 in three patients (in one of them used concomitantly); ipilimumab was the most frequently used ICI (11/23) Table 1).…”

“…Six patients developed atypical demyelination and did not fit into previous diagnostic groups (14,25,(46)(47)(48)(49). Imaging patterns were typical for MS in two cases, with periventricular white matter lesions with incomplete gadolinium enhancement (patient 19) and small non-enhancing periventricular and spinal cord white matter lesions (patient 21).…”

Exploring the VISTA of microglia: immune checkpoints in CNS inflammation

“…Interestingly, ICI used in oncology have adverse effects on the CNS. Nivolumab treatment of melanoma induced spontaneous, reversible CNS demyelination in a patient [ 106 ]. ICI-treated patients are also more susceptible to developing other CNS diseases including paraneoplastic neurological symptoms, encephalitis, MS and hypophysitis, an inflammation of the pituitary gland [ 1 ].…”