Neuroimmunological adverse events associated with immune checkpoint inhibitor: a retrospective, pharmacovigilance study using FAERS database

Mikami, Takahisa; Liaw, Bobby Chi-Hung; Asada, Mizuho; Niimura, Takahiro; Zamami, Yoshito; Green-LaRoche, Deborah; Pai, Lori; Lévy, Michaël; Jeyapalan, Suriya

doi:10.1007/s11060-020-03687-2

Cited by 55 publications

(69 citation statements)

References 22 publications

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“…Vasculitis-type IRAEs are rare with less than 1% incidence, the most common of which are of large vessels (for example giant cell arteritis and aortitis) or central nervous system vasculitis [ 7 ]. A recent FDA Adverse Event Reporting System (FAERS) retrospective study of neurological IRAEs across multiple cancer types including small numbers of patients with mesothelioma, reported an increased risk with combined ICI therapy compared to monotherapy, but interestingly not in cases associated specifically with vasculitis [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma

et al. 2022

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Background Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with an overall poor prognosis. In October 2020, first line treatment with the PD-1 antagonist nivolumab and the CTLA-4 antagonist ipilimumab for unresectable disease was FDA approved—the first approved treatment regime since 2004. Interim analyses from the phase 3 CHECKMATE-743 study shows improvements in overall survival. Skin-related toxicities are the most commonly reported any-grade treatment-related adverse event from combined nivolumab and ipilimumab therapy. Case presentation Here we report a case of a 35-year-old white male who developed digital ischaemia secondary to small vessel vasculitis after receiving PD-1 and CTLA-4 blockade therapy for MPM. His progressive ischaemia became gangrenous, and he required multi-speciality input and treatment with prednisolone, prostacyclin, mycophenolate mofetil and hydroxychloroquine. Conclusions Our case highlights the importance of early detection, intervention, and a multispecialty approach to managing such complications in order to minimise the associated morbidity and mortality.

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Section: Discussionmentioning

confidence: 99%

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma

et al. 2022

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“…This suggests that many neurological irAEs might be underreported. This might be attributable to their non-specific symptoms, their low incidence, and a lack of recognition of these irAEs among oncologists ( 36 , 37 ).…”

Section: Discussionmentioning

confidence: 99%

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Lu²,

Tang³

et al. 2022

Front. Oncol.

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BackgroundImmune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), but there is limited evidence regarding the association between urinary incontinence and ICIs.MethodsWe described the case of a patient experiencing urinary incontinence who later experienced a series of irAEs such as myocarditis, myositis, and neurologic diseases while on ICI treatment in our hospital. In addition, we queried the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the third quarter of 2010 to the third quarter of 2020 to perform a retrospective study to characterize the clinical features of urinary incontinence associated with ICIs.ResultIn the FAERS study, 59 cases of ICI-related urinary incontinence were retrieved, and approximately 32.2% of the cases were fatal. Combination therapy with nervous system drugs and age >80 years old were the significant risk factors for fatal outcomes. Among these cases of ICI-related urinary incontinence, 40.7% (n = 24) occurred concomitantly with other adverse events, especially, neurological (fifteen cases), cardiovascular (seven cases), musculoskeletal (six cases), and urological disorders (five cases). Five cases had an overlapping syndrome similar to our case report, including one case of myasthenia gravis with myocarditis and another of myasthenic syndrome with polymyositis.ConclusionICI-related urinary incontinence might be a signal of fatal neuromuscular irAEs, especially when it occurs concomitantly with ICI-associated neuromuscular–cardiovascular syndrome. Clinicians should be aware of the occurrence of urinary incontinence to identify potentially lethal irAEs in the early phase.

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“…In addition, the response rate of melanoma to ICIs was higher than other tumors [ 54 ]. A FAERS database-based clinical study also showed that patients with melanoma or non-small-cell lung cancer maybe at higher risk of fatal neurologic AEs [ 55 ]. Therefore, the author speculated that melanoma patients were more likely to develop GBS after ICI treatment than other types of tumors.…”

Section: Discussionmentioning

confidence: 99%

Guillain-Barré Syndrome-Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases

Zhang

Zhao

2021

BioMed Research International

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Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of various types of tumors with favorable results. But these treatments also led to a variety of immune-related adverse events (irAEs). Neurological irAEs such as Guillain-Barré Syndrome are rare and may have serious consequences once they occur. A systematic literature search was performed in PubMed and Embase for all case reports of GBS associated with ICIs published in English reporting on human beings from 1990 up to date. A total of 30 case reports ( total patients = 33 ) were used for final analysis. The included cases were from 11 countries, covering 10 tumor types, with melanoma accounting for the largest number. The mean age was 62.2 ± 11.1 years old, and males were dominant (male: 26 and female: 7). The median time of initial symptoms was 8.2 weeks after the 1st dose of ICIs. The most common manifestations of GBS associated with ICIs were weakness, hyporeflexia or areflexia, and paresthesia in order. The GBS subtypes suggested by electrophysiological results were acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and Miller Fisher syndrome (MFS). The protein level of CSF in patients with GBS related to ICIs was 180.68 ± 152.51 mg/dl. Immediate termination of ICIs followed by intravenous immunoglobulin was the preferred treatment option. 72.7% of patients recovered or had residual mild dysfunction after treatment. Elderly male patients with melanoma were most likely to develop ICI-related GBS. The specific neurological symptoms, CSF analysis, and electrophysiological examination were important means of diagnosis.

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Neuroimmunological adverse events associated with immune checkpoint inhibitor: a retrospective, pharmacovigilance study using FAERS database

Cited by 55 publications

References 22 publications

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma

Small vessel vasculitis and dry gangrene secondary to combined CTLA-4 and PD-1 blockade in malignant mesothelioma

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study

Guillain-Barré Syndrome-Like Polyneuropathy Associated with Immune Checkpoint Inhibitors: A Systematic Review of 33 Cases

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