Neurological immune-related adverse events of ipilimumab

Bot, Ilja; Blank, Christian U.; Boogerd, Willem; Brandsma, Dieta

doi:10.1136/practneurol-2012-000447

Cited by 123 publications

(92 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to hypophysitis, neurological side effects of the checkpoint inhibitors include very few or single cases of aseptic meningitis, GBS, and myositis 5, 15. More recently, 0.1% of patients administered nivolumab were reported to develop MG.…”

Section: Discussionmentioning

confidence: 99%

“…However, immune‐related adverse events (irAEs) affect up to 40% of patients treated with checkpoint inhibitors and include colitis, dermatitis, pneumonitis, and hepatitis 4. More rarely, neurological side effects are observed: the most frequent is hypophysitis 5. While conventional models typically suggest irAEs are T cell mediated, here, we describe likely antibody‐mediated autoimmunity with the first case of immune checkpoint‐blockade associated with longitudinally extensive transverse myelitis (LETM, n = 1), and cases who developed myasthenia gravis (MG, n = 2) and Guillain–Barré syndrome (GBS, n = 1) after checkpoint inhibitors.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Seronegative antibody‐mediated neurology after immune checkpoint inhibitors

Wilson

Menassa

Davies

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Checkpoint inhibitor medications have revolutionized oncology practice, but frequently induce immune‐related adverse events. During autoimmune neurology practice over 20 months, we prospectively identified four patients with likely antibody‐mediated neurological diseases after checkpoint inhibitors: longitudinally extensive transverse myelitis, Guillain–Barré syndrome, and myasthenia gravis. All patients shared three characteristics: symptoms commenced 4 weeks after drug administration, responses to conventional immunotherapies were excellent, and autoantibodies traditionally associated with their syndrome were absent. However, serum immunoglobulins from the myelitis and Guillain–Barré syndrome patients showed novel patterns of tissue reactivity. Vigilance is required for antibody‐mediated neurology after checkpoint inhibitor administration. This phenomenon may inform the immunobiology of antibody‐mediated diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Seronegative antibody‐mediated neurology after immune checkpoint inhibitors

Wilson

Menassa

Davies

et al. 2018

Ann Clin Transl Neurol

View full text Add to dashboard Cite

show abstract

“…Melanocytes and Schwann cells are derived from the neural crest and share similar antigens [41][42][43]. Gangliosides expressed on melanocytes are highly immunogenic with subsequent antibody formation which may be responsible for initiating peripheral motor sensory neuropathies such as Guillain Barre Syndrome [41,43].…”

Section: Neurological Toxicitymentioning

confidence: 99%

“…MRI spine and/or brain, nerve conduction studies and lumbar puncture may facilitate the diagnosis [41,43,45]. Plasmapheresis or intravenous immunoglobulin or supportive drugs such as pyridostigmine in the case of Myasthenia Gravis, may be required in cases which are refractory to corticosteroids [41,43,44]. In addition, in persistent grade 2 or severe cases, ICPI should be permanently discontinued [10,41,[49][50][51].…”

mentioning

confidence: 99%

“…Gangliosides expressed on melanocytes are highly immunogenic with subsequent antibody formation which may be responsible for initiating peripheral motor sensory neuropathies such as Guillain Barre Syndrome [41,43]. 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] Acute management includes discontinuation of ICPI and early administration of either oral prednisolone or IV methylprednisolone (1-2 mg/kg/day), depending on the severity of the symptoms, [41,43,45] which may result in complete neurological recovery [48]. Early specialist neurological assessment is also advised [7].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Untitled

2016

JCPCR

View full text Add to dashboard Cite

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...

show abstract