Nivolumab induced immune mediated transverse myelitis in a patient with metastatic melanoma: The broad clinical spectrum of immune mediated neurologic disorders

Bover, Mateo; Otero, Irene; Yarza, Ramón

doi:10.1016/j.cpccr.2021.100076

Cited by 4 publications

(6 citation statements)

References 17 publications

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“…As a result of an enhanced immune response, ICI may cause a variety of autoinflammatory disorders in susceptible individuals, known as immune related adverse events (irAEs). Neurologic irAEs are estimated to occur in up to five percent of patients with ICIs and clinical manifestations can include autoimmune encephalitis, Gullian-Barré-like syndrome, motor/sensory and autonomic peripheral neuropathies, myasthenia gravis-like syndrome, posterior reversible encephalopathy syndrome, aseptic meningitis and transverse myelitis ( 3 , 7 ). Whilst neurological irAEs represent a relatively small proportion of all reported irAEs with ICIs, they embody a heterogeneous group that can often present insidiously, have a vast array of differential diagnoses (including progressive malignancy) and can result in severe disability or death, and therefore are perhaps the most challenging irAEs to detect and treat.…”

Section: Discussionmentioning

confidence: 99%

“…With their advent, there has also been increasing acknowledgment of complications of ICIs in the form of immune-related adverse events (irAEs) ( 2 ). Neurological irAEs are thought to account for1–5% of all irAEs ( 3 ). Diagnosing neurological irAEs can be challenging due to their often subtle presentations and varying severities, and in the absence of prompt identification and implementation of treatment, can lead to significant disability or mortality.…”

Section: Introductionmentioning

confidence: 99%

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Case series: Immune checkpoint inhibitor-induced transverse myelitis

Chatterton

Xi²,

Jia³

et al. 2023

Front. Neurol.

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IntroductionIncreasing implementation of the highly efficacious immune checkpoint inhibitors (ICIs) has raised awareness of their various complications in the form of immune-related adverse events (irAEs). Transverse myelitis following ICIs is thought to be a rare but serious neurologic irAE and knowledge is limited about this distinct clinical entity.CasesWe describe four patients across three tertiary centers in Australia with ICI-induced transverse myelitis. Three patients had a diagnosis of stage III–IV melanoma treated with nivolumab and one patient had stage IV non-small cell lung cancer treated with pembrolizumab. All patients had longitudinally extensive transverse myelitis on magnetic resonance imaging (MRI) spine and clinical presentation was accompanied by inflammatory cerebrospinal fluid (CSF) findings. Half of our cohort had received spinal radiotherapy, with the areas of transverse myelitis extending beyond the level of previous radiation field. Inflammatory changes on neuroimaging did not extend to the brain parenchyma or caudal nerve roots, except for one case involving the conus medullaris. All patients received high dose glucocorticoids as first-line therapy, however the majority relapsed or had a refractory state (3/4) despite this, requiring escalation of their immunomodulation, with either induction intravenous immunoglobulin (IVIg) or plasmapheresis. Patients in our cohort who relapsed had a poorer outcome with more severe disability and reduced functional independence following resolution of their myelitis. Two patients had no progression of their malignancy and two patients had malignancy progression. Of the three patients who survived, two had resolution of their neurological symptoms and one remained symptomatic.ConclusionWe propose that prompt intensive immunomodulation is favored for patients with ICI-transverse myelitis in an attempt to reduce associated significant morbidity and mortality. Furthermore, there is a significant risk of relapse following cessation of immunomodulatory therapy. We suggest one treatment approach of IVMP and induction IVIg for all patients presenting with ICI-induced transverse myelitis based on such findings. With the increasing use of ICIs across oncology, further studies are required to explore this neurological phenomenon in greater detail to help establish management consensus guidelines.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Case series: Immune checkpoint inhibitor-induced transverse myelitis

Chatterton

Xi²,

Jia³

et al. 2023

Front. Neurol.

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“…Furthermore, Bover et al noted nivolumab-induced transverse myelitis in a patient with metastatic melanoma. The patient showed progressive intentional tremors on both the upper and lower limbs and marked improvement of neurological symptoms with intravenous methylprednisolone [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report

Park

Kim

2023

BMC Neurol

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Background Nivolumab is an immune checkpoint inhibitor that targets the programmed cell death-1 protein and is effective in treating advanced cancer. However, it is also associated with various immune-related neurological complications, including myasthenia gravis, Guillain–Barré syndrome, and demyelinating polyneuropathy. These complications can easily mimic other neurological diseases and have greatly varying therapeutic approaches depending on the underlying pathophysiology. Case presentation Here, we report a case of nivolumab-induced demyelinating peripheral polyneuropathy involving the brachial plexus in a patient with Hodgkin lymphoma. Approximately 7 months after nivolumab treatment, the patient experienced muscle weakness with a tightness and tingling sensation in the right forearm. Electrodiagnostic studies showed features of demyelinating peripheral neuropathy with right brachial plexopathy. Magnetic resonance imaging revealed thickening with a diffuse enhancement of both brachial plexuses. The patient was eventually diagnosed with nivolumab-induced demyelinating polyneuropathy involving the brachial plexus. Oral steroid therapy improved motor weakness and sensory abnormalities without aggravation. Conclusion Our study indicates the possibility of nivolumab-induced neuropathies in cases involving muscle weakness with sensory abnormalities of the upper extremity following nivolumab administration in patients with advanced cancer. Comprehensive electrodiagnostic studies and magnetic resonance imaging are helpful in the differential diagnosis of other neurological diseases. Appropriate diagnostic and therapeutic approaches may prevent further neurological deterioration.

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“…Nearly all affected individuals develop motor weakness in the lower limbs, tactile/thermic sensory disturbances, paresthesias, proprioceptive ataxia, and sphincter dysfunction. In most cases, spinal MRI reveals extensive longitudinal lesions (>3 segments in length) and variable contrast enhancement on brain and spinal MRI scans (diffuse hyperintensities on the spinal cord, brain parenchyma, meninges, and cauda equina roots) [ 74 , 75 ]. In CSF analysis, pleocytosis, elevated protein levels, and oligoclonal bands are usually present in up to 50% of cases; this finding may be helpful in the differential diagnosis between ICI-mediated myelitis and chemotherapy-induced myelopathy [ 75 ].…”

Section: Clinical Presentation Of Post-ici Neurotoxicitymentioning

confidence: 99%

Neurological Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors

Stavropoulou De Lorenzo,

Andravizou,

Alexopoulos

et al. 2024

Biomedicines

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The use of immune checkpoint inhibitors (ICIs) for the treatment of various advanced and aggressive types of malignancy has significantly increased both survival and long-term remission rates. ICIs block crucial inhibitory pathways of the immune system, in order to trigger an aggravated immune response against the tumor. However, this enhanced immune activation leads to the development of numerous immune-related adverse events (irAEs), which may affect any system. Although severe neurological irAEs are relatively rare, they carry a high disability burden, and they can be potentially life-threatening. Therefore, clinicians must be alert and act promptly when individuals receiving ICIs present with new-onset neurological symptoms. In this narrative review, we have collected all the currently available data regarding the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of post-ICI neurological irAEs. This review aims to raise physicians’ awareness, enrich their knowledge regarding disease pathogenesis, and guide them through the diagnosis and management of post-ICI neurological irAEs.

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Nivolumab induced immune mediated transverse myelitis in a patient with metastatic melanoma: The broad clinical spectrum of immune mediated neurologic disorders

Cited by 4 publications

References 17 publications

Case series: Immune checkpoint inhibitor-induced transverse myelitis

Case series: Immune checkpoint inhibitor-induced transverse myelitis

Demyelinating polyneuropathy combined with brachial plexopathy after nivolumab therapy for hodgkin lymphoma: a case report

Neurological Immune-Related Adverse Events Induced by Immune Checkpoint Inhibitors

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