Delayed onset of neurosarcoidosis after concurrent ipilimumab/nivolumab therapy

Abstract

BackgroundImmune checkpoint inhibitors have transformed the treatment landscape for many cancers, including metastatic melanoma, but have also opened the door for a diverse variety of immune-related adverse effects.Case presentationWe describe the first reported case of presumed neurosarcoidosis as an immune-related adverse effect that developed nearly a year after discontinuation of treatment with combination ipilimumab and nivolumab for recurrent metastatic melanoma. The patient was noted to develop clinical signs consistent with systemic sarcoidosis shortly after the initiation of treatment and underwent a biopsy of hilar lymphadenopathy that confirmed sarcoidosis and after which immunotherapy was discontinued. His melanoma remained stable on surveillance imaging for the next year after which time he developed neurological symptoms and was found to have MRI brain abnormalities without evidence of intracranial metastatic disease, consistent with probable neurosarcoidosis given biopsy-proven systemic sarcoidosis and lack of evidence of CNS infection or malignancy. He underwent treatment with high dose steroids, followed by infliximab, and then methotrexate with both clinical and radiographic improvement within 4 months of starting treatment.ConclusionsImmune-related adverse effects often occur within 3–6 months of receiving immune checkpoint inhibitor therapy, with some reports of late toxicity. This report highlights a case of probable neurosarcoidosis nearly a year after discontinuation of immune checkpoint therapy. The potential for durable responses after discontinuation of therapy also likely underscores a potential for late toxicity. In patients presenting with new or unexplained symptoms after checkpoint inhibitor therapy, the index of suspicion for an immune-related adverse effect should remain high, irrespective of timing.

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

“…89 Other systemic manifestations have been described, including sarcoidosis or sarcoid-like reactions. [90][91][92][93] The diagnosis is usually suspected through imaging when new hilar lymphadenopathy or pulmonary nodules are detected in imaging, requiring biopsy. Half of patients experienced cutaneous manifestations (nodules, rash), and some patients had cough/dyspnoea (29%) and arthralgia/arthritis (18%).…”

Neurological immune‐related adverse events associated with immune checkpoint inhibitors: A review of the literature

“…4,24 The most common irAEs of the CNS includes encephalitis, aseptic meningitis, and myelitis. Some irAEs of the CNS are extremely rare, such as multiple sclerosis (MS), 25 posterior reversible encephalopathy syndrome, 26 neurosarcoidosis, 27 cerebral vasculitis, 28 Tolosa-Hunt syndrome, 29 and Vogt-Koyanagi-Harada syndrome. 30 Given the high fatality rate of irAEs of the CNS (encephalitis, 6.3-12.8%; meningitis, 7.4-8.3% 19,20 ), patients should be recognized promptly and treated with immune-modulating agents without delay.…”

Rheumatic Manifestations in Patients Treated with Immune Checkpoint Inhibitors

“…New-onset sarcoidosis has been mainly reported in association with melanoma [84], with a prevalence of 0.2% according to the nationwide multicenter registry in France, the Registry of Severe Adverse Reactions to Immunomodulatory Antibodies in Oncology (REISAMIC) [28]. ICI-induced sarcoidosis can present as cutaneous sarcoidosis [85] or systemic with lymphadenopathy, lung [86] or neurological and ocular involvement [87][88][89][90]. There are no specific serum findings for ICI-induced sarcoidosis.…”