Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature

Spain, Lavinia; Walls, G.; Julve, Maximilian; O'Meara, Karen; Schmid, Thomas; Kalaitzaki, E.; Turajlic, Samra; Gore, Martin; Rees, Jeremy; Larkin, James

doi:10.1093/annonc/mdw558

Cited by 229 publications

(223 citation statements)

References 12 publications

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“…Drug‐induced aseptic meningitis is a rare adverse event that has been reported with various pharmaceutical products, including nonsteroidal anti‐inflammatory drugs, antimicrobials, iv immunoglobulin (IVIG), vaccines, and most recently, ICIs . Patient 1 denied use of these agents, and there are no data supporting a link between cabozantinib and aseptic meningitis.…”

Section: Discussionsupporting

confidence: 38%

“…The reported median time to onset of neurologic irAEs is 6 weeks . Onset of meningitis‐associated symptoms in our patient was much later compared to previously published reports (24 doses vs 1‐2 doses, respectively) . Drug‐induced aseptic meningitis may be self‐limited and resolve without treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Drug‐induced aseptic meningitis may be self‐limited and resolve without treatment. Case reports of aseptic meningitis associated with ICIs have also demonstrated spontaneous symptom resolution . Current guidelines recommend monitoring of steroids or considering steroids for moderate/severe symptoms or unwell patients .…”

Section: Discussionmentioning

confidence: 99%

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Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature

Cordes

Davarpanah

Reoma

et al. 2019

Clinical Case Reports

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Section: Discussionsupporting

confidence: 38%

Section: Discussionmentioning

confidence: 99%

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Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature

Cordes

Davarpanah

Reoma

et al. 2019

Clinical Case Reports

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“…Early recognition and management of neurological irAEs is essential for maximizing clinical recovery and minimizing effect of drug-related toxicity. Although irAEs can occur at any stage of treatment, presentations within 4 months of treatment initiation is typical [44] as was seen in both these patients. Management of suspected neurological irAEs should incorporate early input of subspecialty neurologists attuned to fully characterize the neurological perturbation and to exclude leptomeningeal and/or paraneoplastic manifestations of cancer particularly in certain malignancies (melanoma, non-small cell lung cancer, etc.).…”

Section: Discussionmentioning

confidence: 99%

Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases

Garcia¹,

El-Ali²,

Rath³

et al. 2018

j. immunotherapy cancer

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BackgroundPD-1 and CTLA-4 inhibitors are associated with several adverse events including a spectrum of immune-related adverse effects (irAEs). Neurologic irAEs are uncommon occurrences with varied presentations. We describe two separate cases of ipilimumab associated meningoencephalomyelitis and demyelinating polyneuropathy with unusual presentations.Case presentationTwo melanoma patients were treated with ipilimumab in the adjuvant setting. The first patient developed a meningoencephalitis following 3 doses of ipilimumab. MRI imaging of the brain confirmed leptomeningeal enhancement although cerebrospinal fluid (CSF) analyses were negative for malignant cells consistent with meningoencephalomyelitis. Although she initially improved following treatment with steroids and intravenous immunoglobulin, she subsequently relapsed. She was successfully treated with infliximab and made a complete neurological recovery. A second patient developed progressive lower extremity weakness following two doses of ipilimumab. MRI imaging of the spine confirmed diffuse nerve root enhancement consistent with acute inflammatory demyelinating polyneuropathy (AIDP). He was treated with high dose steroids with resolution of neurological symptoms. Both patients remain disease free.ConclusionsNeurological irAEs are uncommon adverse events in the context of CTLA-4 and/or PD-1 inhibitor therapy. Care must be taken to distinguish these from leptomeningeal disease. Early recognition of neurological irAEs is critical for the initiation of specific anti-inflammatory agents to prevent and potentially reverse neurological sequelae.

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“…It is postulated that neurological toxicity can occur in about 1-3% of patients from literature reviews [46]. Most information collected about neurological toxicity from immunotherapy is from case reports.…”

Section: Neurologicalmentioning

confidence: 99%

Management and Supportive Care of Patients Undergoing Immunotherapy

Rapoport¹,

Eeden²

2017

Immunotherapy - Myths, Reality, Ideas, Future

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In many tumor types, where the prognosis was shown to be extremely dismal before, immunotherapy is now a new beacon of hope to many patients. Immunotherapy has been approved for use in a many diferent cancers including metastatic melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, refractory Hodgkin's lymphoma, metastatic bladder cancer advanced head and neck cancer, and the list keeps growing each day. It seems to be generally beter tolerated in most patients and less toxic compared to what we have seen in diferent anticancer treatments from before. However, the toxicities here are termed immune-related adverse events. There is almost no prospective data on these toxicities, and guidelines or recommendations are mostly based on symptomatic management from the ongoing clinical trials. Treating oncologists need to be aware of the subtleties in presentation and the huge diference in the way we mange these side efects. Although most adverse events are low-grade and manageable, they have the potential to be life-threatening if not treated promptly. In this chapter, we address the diferent immune-related adverse events relating to the organ system they can involve, presentation and symptomatology, general recommendations of management, and individual toxicities. Keywords: immunotherapy, PD-1, CTLA-4.

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Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature

Abstract: Neurological toxicity is not uncommon, and may be more frequent in patients treated with combination ipi + nivo. Patterns of presentation and response to treatment are varied. A prompt and considered approach is required to optimize outcomes in this group of patients.

Cited by 229 publications

References 12 publications

Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature

Neurotoxicities associated with checkpoint inhibitors: Two case reports and a review of the literature

Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases

Management and Supportive Care of Patients Undergoing Immunotherapy

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