Encephalomyeloneuritis and arthritis after treatment with immune checkpoint inhibitors

Abstract

ObjectiveImmunotherapy revolutionized melanoma treatment; however, immune-related adverse events, especially neurotoxicity, may be severe and require early and correct diagnosis as well as early treatment commencement.MethodsWe report an unusual severe multiorgan manifestation of neurotoxicity after treatment with the anti-PDL1 immune checkpoint inhibitor, nivolumab, and the anticytotoxic T-lymphocyte-associated antigen 4 immune checkpoint inhibitor, ipilimumab, in a 47-year-old male patient with metastatic melanoma.ResultsThe patient developed immune-mediated synovitis and cranial neuritis, followed by longitudinal transverse myelitis, encephalitis, and optic neuritis. Early treatment with high-dose steroids and maintenance therapy with rituximab resulted in a favorable neurologic outcome.ConclusionsThe frequency of spinal cord involvement and neuronal toxicity after cancer immunotherapy is very low and requires an extensive diagnostic workup to differentiate between disease progression and side effects. Immune checkpoint inhibitors should be discontinued and treatment with corticosteroids should be initiated early as the drug of first choice. Therapy may be escalated by other immune-modulating treatments, such as rituximab.

Detect it so you can treat it: A case series and proposed checklist to detect neurotoxicity in checkpoint therapy

“…Wilson et al [ 28 ] presented a case of longitudinally extensive transverse myelitis after pembrolizumab treatment in which the patient improved after the intravenous administration of corticosteroids, immunoglobulins and plasma exchange. Further cases have been described [ 29 , 30 ]. Common autoantibody profiles associated with extensive transverse myelitis, such as aquaporin-4 and myelinoligodendrocyte glycoprotein antibodies, were not detected.…”

Immune-Related Uncommon Adverse Events in Patients with Cancer Treated with Immunotherapy

“…Non-granulomatous uveitis and dry eye syndrome are by far the most common ocular adverse events, presenting in a frequency ranging from 0.3 to 6% and 1.2 to 24%, respectively [ 225 ]. Optic neuritis [ 226 ], neuromyelitis optica with positive anti-aquaporin-4 antibodies [ 227 , 228 , 229 , 230 ], and even encephalomyeloneuritis [ 231 ] have also been reported. The average timing of irAEs from starting checkpoint inhibitor therapy is approximately 15 weeks [ 232 ].…”

Evaluation and management of acute high-grade immunotherapy-related neurotoxicity

“…The resulting nerve damage causes varying degrees of weakness, sensory loss, and autonomic dysfunction. Checkpoint inhibitors have been associated with acute transverse myelitis in case reports and series [ 73 , 107 , 117 , [124] , [125] , [126] , [127] , [128] , [129] ].…”