A Severe Case of Ipilimumab-Induced Guillain-Barré Syndrome Revealed by an Occlusive Enteric Neuropathy

Gaudy‐Marqueste, C.; Monestier, S.; Franques, Jérôme; Cantais, E.; Richard, M.‐A.; Grob, Jean-Jacques

doi:10.1097/cji.0b013e31827807dd

Cited by 90 publications

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“…Neurologic manifestations of irAE's are extremely rare. A few cases of ipilimumab-induced Guillain-Barré syndrome (GBS) have been reported in the literature (Gaudy-Marqueste et al 2013;Wilgenhof and Neyns 2011). To our knowledge, this is the first case of nivolumab-induced GBS.…”

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confidence: 89%

A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use

Jacob

Unnikrishnan

Mathew

et al. 2016

J Cancer Res Clin Oncol

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on ventilator support. Unfortunately, her clinical condition did not improve and she was extubated after 11 days. She expired in hospice care within a few hours.Immune checkpoint inhibitors modulate the immune system and may cause immune-related adverse events (irAE) (Naidoo et al. 2015). Neurologic manifestations of irAE's are extremely rare. A few cases of ipilimumab-induced Guillain-Barré syndrome (GBS) have been reported in the literature (Gaudy-Marqueste et al. 2013;Wilgenhof and Neyns 2011). To our knowledge, this is the first case of nivolumab-induced GBS. Immune response directed against the myelin or axon of the peripheral nerve is implicated in the pathogenesis of GBS (Yuki and Hartung 2012). Nivolumab can cause disruption in normal immune checkpoint molecule function resulting in decreased peripheral tolerance to ganglioside-related epitopes and unchecked immune responses (Csurhes et al. 2005). With increasing use of nivolumab in advanced malignancies, physicians should be aware of rare adverse events like GBS, which can be effectively treated with rapid initiation of corticosteroids, IVIG or plasma exchange along with discontinuation of anti-PD1 antibody therapy. Compliance with ethical standardsConflict of interest None. ReferencesCsurhes PA, Sullivan A-A, Green K, Greer JM, Pender MP, McCombe PA (2005) Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain-Barré syndrome. J Clin Neurosci 12(4):409-415 Gaudy-Marqueste C, Monestier S, Franques J, Cantais E, Richard M-A, Grob J-J (2013) A severe case of ipilimumab-inducedEditor, A 68-year-old woman with stage III squamous cell carcinoma of the lung was treated with carboplatin, nabpaclitaxel, and concurrent radiation. A year later, she was diagnosed with brain metastases and nivolumab, an anti-PD1 monoclonal antibody, was initiated at a dose of 3 mg/ kg given every 2 weeks. Three months later, she presented with fatigue and bilateral lower extremity weakness of 4 days duration. Her most recent dose of nivolumab was administered 9 days ago. Physical examination revealed decreased strength in both legs. A CT scan of the brain revealed partial response to nivolumab therapy. An MRI scan of the spine was normal. Twelve hours later, she reported tingling sensation in her feet and profound weakness in lower extremities. Soon, she experienced progressive loss of motor and sensory function in arms and legs. Physical examination revealed loss of deep tendon reflexes in all four extremities associated with complete lack of strength. Cerebrospinal fluid (CSF) analysis showed clear appearance, with no nucleated cells, normal glucose and elevated protein levels (85 mg/dL; normal range 15-45). CSF Gram stain test, microbiological cultures and herpes simplex virus (HSV) DNA test were negative. The clinical finding of acute areflexic paralysis and the CSF finding of albuminocytologic dissociation were consistent with a diagnosis of GBS. She was started on intravenous immunoglobulin (IVIG) and plasma exchange. Within 2 hours, she developed ...

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confidence: 89%

A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use

Jacob

Unnikrishnan

Mathew

et al. 2016

J Cancer Res Clin Oncol

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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.…”

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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“…Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients with metastatic melanoma, 5 but can cause severe irAEs. 6,7 The appropriate management of irAEs is critical as side effects can be fatal. 7 Gastrointestinal irAEs are seen most commonly in up to 31% and hepatic irAEs in 3%-9% of patients.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 The appropriate management of irAEs is critical as side effects can be fatal. 7 Gastrointestinal irAEs are seen most commonly in up to 31% and hepatic irAEs in 3%-9% of patients. 1 This patient with a severe grade 3 diarrhea was treated with high-dose prednisone as per algorithm 8 and as symptoms persisted with infliximab.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With Ipilimumab

Uslu¹,

Agaimy

Hundorfean³

et al. 2015

Journal of Immunotherapy

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Ipilimumab, a humanized CTLA-4 antibody, improves overall survival in patients with metastatic melanoma. However, immune-related adverse effects occur in about 65% of ipilimumab-treated patients and have to be adequately managed. A 55-year-old patient developed grade 3 autoimmune colitis 7 weeks after initiation of ipilimumab treatment and subsequently hepatitis with grade 3 elevation of transaminases and γ-glutamyl transferase. Colitis manifested with up to 18 watery and bloody stools per day and severe attacks of abdominal pain. After exclusion of infectious causes, immunosuppression with corticosteroids was initiated. Because of recurrent abdominal pain, spontaneous perforation of the colon had to be excluded. Elevated liver function tests (grade 3 CTCAE) occurred and differential diagnosis included immune-mediated, toxic, and viral hepatitis. It is interesting to note that, not an immune-mediated but a cytomegalovirus-induced hepatitis was diagnosed by serum blood tests and liver biopsy and was subsequently successfully treated. Careful elaboration of the patient under immunotherapy was essential as further immunosuppression mandatory for autoimmune hepatitis would have worsened the viral hepatitis. In conclusion, cytomegalovirus reactivation should be included in the differential in patients under immunotherapy with checkpoint inhibitors and has to be considered as a cause for morbidity.

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A Severe Case of Ipilimumab-Induced Guillain-Barré Syndrome Revealed by an Occlusive Enteric Neuropathy

Cited by 90 publications

References 0 publications

A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use

A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use

Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma

Autoimmune Colitis and Subsequent CMV-induced Hepatitis After Treatment With Ipilimumab

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