Multifocal radiculoneuropathy during ipilimumab treatment of melanoma

Manousakis, Georgios; Koch, James P.; Sommerville, R. Brian; El-Dokla, Ahmed; Harms, Matthew B.; Al-Lozi, Mbbs Muhammad T.; Schmidt, Robert E.; Pestronk, Alan

doi:10.1002/mus.23830

Cited by 69 publications

(39 citation statements)

References 25 publications

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“…For example, IrAEs for ipilimumab include Guillain-Barr e syndrome (16)(17)(18), multifocal radiculoneuropathy, and chronic inflammatory demyelinating polyneuropathy (19). In a case report for a patient with nerve pathology (17), the biopsy showed inflammation around endoneurial microvessels and subperineurial edema and inflammation. A patient on ipilimumab developed mild encephalopathy with a lesion in the splenium of the corpus callosum (2) that resolved after treatment with methylprednisolone.…”

Section: T Cells Often Express High Amounts Of Pd-1 Suggesting That mentioning

confidence: 99%

Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma

Maurice

Schneider

Kiehl

et al. 2015

Cancer Immunology Research

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Immunotherapy with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) has improved the survival of patients with metastatic melanoma. These agents carry a certain risk of adverse immune-related events. We present a patient with widely metastatic melanoma who was initially treated with ipilimumab and subsequently with nivolumab. After four infusions of nivolumab, he developed subacute multifocal central nervous system (CNS) demyelination. Nivolumab was discontinued and, despite immunosuppressive therapy, the largest lesion progressed significantly, whereas another lesion showed radiographic improvement. After further progression, the patient succumbed to his CNS lesions 4 months later. Autopsy revealed extensive demyelination, a mild multifocal T-cell-rich perivascular lymphoid infiltrate, abundant macrophages, and necrosis. There was no metastatic melanoma in the brain. CNS demyelination has not been described in association with nivolumab. We hypothesize that the combination therapy of ipilimumab and subsequent nivolumab accounted for the severity of the demyelinating process in this patient. This case, with comprehensive clinical, molecular, and neuropathologic characterization, illustrates the need for awareness of these potential CNS complications with the use of multiple checkpoint inhibitors.

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Section: T Cells Often Express High Amounts Of Pd-1 Suggesting That mentioning

confidence: 99%

Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma

Maurice

Schneider

Kiehl

et al. 2015

Cancer Immunology Research

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“…Although cranial nerve involvement [5] has been described previously, mononeuropathy involving both phrenic nerves after administration of ipilimumab has not been previously reported. The exact mechanism is not known, but inflammation around endoneurial microvessels with subperineurial edema has been reported.…”

Section: Discussionmentioning

confidence: 87%

“…(histiocytic) cells. Disruption of the blood-nerve barrier with microvasculopathy could be the cause for neuropathy [5]. Partial to complete recovery of neurological functions, and favorable response to immunosuppression with corticosteroids has been reported in majority of the previously reported cases [5][6][7][8].…”

Section: Discussionmentioning

confidence: 97%

“…Immune-related neurological adverse effects reported include sensorimotor neuropathy [3], Guillain-Barré syndrome [4], multifocal radiculoneuropathy [5], aseptic meningitis [6], posterior reversible encephalopathy syndrome [7], myasthenia gravis-type syndrome [8], and inflammatory enteric neuropathy [9]. Although cranial nerve involvement [5] has been described previously, mononeuropathy involving both phrenic nerves after administration of ipilimumab has not been previously reported.…”

Section: Discussionmentioning

confidence: 98%

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Severe Acute Orthopnea: Ipilimumab-Induced Bilateral Phrenic Nerve Neuropathy

Jinnur

Lim

2015

Lung

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Ipilimumab is a monoclonal antibody used in the treatment of unresectable or metastatic melanoma. Several immune-related adverse events including potential fatal events have been reported following its use. We report a case of a 66-year-old man who presented with severe acute exertional dyspnea and orthopnea following administration of ipilimumab for metastatic melanoma. Although various peripheral neuropathy syndromes associated with ipilimumab have been reported, bilateral phrenic nerve paralysis has not been previously reported. This case also highlights the clinical features of bilateral phrenic nerve neuropathy. Pulmonologists have to be aware of these unusual immune-related respiratory adverse events in patients being treated with monoclonal antibodies.

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“…Also, in patients with ICPIinduced encephalitis, N-methyl-D-aspartate receptor (NMDAR) immunoglobulin G antibodies were detected in the cerebrospinal fluid which are also expressed on melanocytes [42,44]. Other neurological irAEs include Myasthenia Gravis-like syndrome [43], posterior reversible leukoencephalopathy [46], aseptic meningitis [21], radiculoneuropathy [47], transverse myelitis [43] and Bell's palsy [40].…”

Section: Neurological Toxicitymentioning

confidence: 99%

Untitled

2016

JCPCR

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Background: Over the last 5 years ever since Ipilimumab received FDA approval for the treatment of metastatic melanoma, immunotherapy as a treatment modality is making its presence felt in oncology clinics across the globe. While initially approved for the treatment of metastatic melanoma alone, the immunotherapy repertoire is ever expanding with its' utility being assessed for in the metastatic and adjuvant setting. The adverse effect profile from immunotherapy drugs differs from that of conventional chemotherapy that oncological services have trained in managing over the last few decades. This raises the need for educating health care professionals as the scenarios that patients present with at acute admissions or in clinic secondary to immune related adverse effects (iRAEs) can often be misleading. Aims:This review aims to synopsise the common and less common iRAEs and highlight their varied presentations, in addition to stressing the need to institute timely immunosuppression, which forms the cornerstone in the management of iRAEs.Recommendations: iRAEs have been recognised more frequently and in greater severity in dose dense and combination treatment regimens. While dermatological, gastrointestinal, hepatic toxicities in addition to endocrinopathies are the most commonly encountered iRAEs though other organ systems can be involved. The appropriate grading of an iRAEs' severity, delaying or discontinuing immunotherapy based treatment, supportive care, commencement of immunosuppression (with corticosteroids and/or steroid sparing agents) and a multidisciplinary approach are key constituents in the treatment pathway of iRAEs. Conclusion:Early recognition of iRAEs and timely commencement of appropriate immunosuppression is imperative in order to reduce the risk of significant morbidity and potential mortality. The management of iRAEs warrants a multidisciplinary approach which would be aided by the development of local guidelines and educational activities directed at providing health care professionals with the information and tools required to recognise and appropriately treat iRAEs. IntroductionOver the last few decades there has been an increasing interest in the field of cancer immunotherapy. The manipulation of the immune system using immunotherapeutic interventions has changed the therapeutic landscape in many type of cancers [1][2][3][4]. However, immunotherapy carries immune-related adverse effects (irAEs) which can be significant [5][6][7]. irAEs are usually reversible but occasionally can be life-threatening [5][6][7]. A retrospective study on the irAEs of Ipilimumab showed that 85% of patients experienced irAEs of any grade of whom 19% discontinued therapy [8]. 35% patients required systemic corticosteroids and 10% required anti-TNF therapy for irAEs [8]. There were no significant differences in overall survival in those with and without irAEs or between those who received corticosteroids or not [8,9]. Hence, this requires the development of treatment protocols and training of the healthcar...

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Multifocal radiculoneuropathy during ipilimumab treatment of melanoma

Abstract: Ipilimumab toxicity presented as a monophasic, multifocal, asymmetric polyradiculoneuropathy involving roots and peripheral and cranial nerves. Ipilimumab may produce a polyradiculoneuropathy with disruption of the blood-nerve barrier due to a microvasculopathy.

Cited by 69 publications

References 25 publications

Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma

Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma

Severe Acute Orthopnea: Ipilimumab-Induced Bilateral Phrenic Nerve Neuropathy

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