Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature

Abdallah, Al‐Ola; Herlopian, Aline; Ravilla, Rahul; Bansal, Meghana; Chandra-Reddy, Sowmya; Mahmoud, Fade; Ong, Shirley; Gökden, Murat; Hutchins, Laura F.

doi:10.1177/1078155215572932

Cited by 38 publications

(42 citation statements)

References 29 publications

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“…Ipilimumab-associated neurological irAEs span diverse entities including severe meningo-radiculo-neuritis [18], reversible splenial lesions [19, 20], hypophysitis [21], meningitis [21], acute cerebellitis [22], Guillain-Barre syndrome [21, 23], myasthenia gravis [24–27], bilateral phrenic nerve paralysis [28], Bell’s palsy [28], chronic inflammatory demyelinating polyneuropathy (CIDP) [29], transverse myelitis [29], encephalitis [30], necrotic myelopathy [31], and partial motor convulsive status (epilepsia partialis continua) [32]. Herein, we report two cases of ipilimumab-associated neurological irAEs manifesting as meningoencephalomyelitis and AIDP respectively.…”

Section: Discussionmentioning

confidence: 99%

“…However, irAE was refractory to steroids, IVIG and infliximab and ultimately required tacrolimus for resolution. In another case report, infliximab (5 mg/kg IV) was given monthly for ipilimumab-induced necrotic myelopathy after lack of response to daily prednisone (1 mg/kg) for 2 weeks [31]. Four weeks after infliximab therapy, she is still wheelchair bound with painful paresthesia.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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“…In addition to these, anti-PD-1 antibodies (pembrolizumab and nivolumab) have been associated with central nervous system toxicity,13 polyneuropathy, cranial nerve paresis and demyelination 2. However, ipilimumab (anti-CLA-4 antibody) has been associated with transverse myelitis,14 15 chronic inflammatory demyelinating polyradiculoneuropathy,14 enteric neuropathy,16 Tolosa-Hunt syndrome,17 aseptic meningitis,17 posterior reversible leukoencephalopathy,18 Bell’s palsy,19 meningo-radiculo-neuritis20 and necrotic myelopathy 21. Pre-existing autoimmune diseases such as multiple sclerosis can also be exacerbated 22.…”

Section: Discussionmentioning

confidence: 99%

Hypothyroid ataxia complicating monoclonal antibody therapy

2017

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“…The paucity of data reflects both the rarity of this disease and concerns about the possibility of inducing “too much” inflammation in the CNS. And, though rare, when they occur, the neurologic side effects associated with the immune checkpoint inhibitors can be devastating …”

Section: Clinical Experience With Immune Therapies In Lmmmentioning

confidence: 99%

Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy

Smalley

Fedorenko

Kenchappa

et al. 2016

Intl Journal of Cancer

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Melanoma frequently metastasizes to the brain, with CNS involvement being clinically evident in ~30% of patients (as high as 75% at autopsy). In ~5% cases melanoma cells also metastasize to the leptomeninges, the sub-arachnoid space and cerebrospinal fluid (CSF). Patients with leptomeningeal melanoma metastases (LMM) have the worst prognosis and are characterized by rapid disease progression (mean survival 8-10 weeks) and a death from neurological causes. The recent years have seen tremendous progress in the development of targeted and immune therapies for melanoma that has translated into an increased survival benefit. Despite these gains, the majority of patients fail therapy and there is a suspicion that the brain and the leptomeninges are a “sanctuary” sites for melanoma cells that escape both targeted therapy and immunologic therapies. Emerging evidence suggests that 1) Cancer cells migrating to the CNS may have unique molecular properties and 2) the CNS/leptomeningeal microenvironment represents a pro-survival niche that influences therapeutic response. In this Mini-Review we will outline the clinical course of LMM development and will describe how the intracranial immune and cellular microenvironments offer both opportunities and challenges for the successful management of this disease. We will further discuss the latest data demonstrating the potential use of BRAF inhibitors and immune therapy in the management of LMM, and will review future potential therapeutic strategies for the management of this most devastating complication of advanced melanoma.

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Ipilimumab-induced necrotic myelopathy in a patient with metastatic melanoma: A case report and review of literature

Cited by 38 publications

References 29 publications

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

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

Hypothyroid ataxia complicating monoclonal antibody therapy

Managing leptomeningeal melanoma metastases in the era of immune and targeted therapy

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