Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

Farina, Antonio; Villagrán-García, Macarena; Ciano-Petersen, Nicolás Lundahl; Vogrig, Alberto; Muñiz‐Castrillo, Sergio; Taillandier, Luc; Michaud, Martine; Lefilliatre, Mathilde; Wang, Adrien; Lepine, Zoe; Picard, Géraldine; Wucher, Valentin; Dhairi, Maroua; Fabien, Nicole; Gonçalves, David; Rogemond, Véronique; Honnorat, Jérôme

doi:10.1212/nxi.0000000000200058

Cited by 20 publications

(20 citation statements)

References 40 publications

(93 reference statements)

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“…When compared to spontaneous PNS, ICI‐triggered PNS more frequently had a multifocal presentation with central and peripheral nervous system involvement, in patients with NET, and in patients with ANNA‐1. In a recent study, ICI‐triggered ANNA‐1 autoimmunity was also associated with manifestations of both central and peripheral nervous system and poorer outcomes in comparison with other neurologic ICI‐triggered autoimmunity [12]. We did not find differences in the outcomes, but this analysis is limited due to small numbers.…”

Section: Discussionmentioning

confidence: 57%

“…As reported in our prior case series [8], the three patients with pre-existing CNS autoimmunity got irreversibly worse despite immunosuppressive treatment. Worsening or relapse of PNS after ICI treatment leading to severe disability has been reported in patients with ANNA-1 PNS [12] and other neurologic and non-neurologic PNS [29,30], suggesting caution in initiating ICI in patients with preexisting PNS.…”

Section: Discussionmentioning

confidence: 99%

“…The CNS paraneoplastic syndromes occurring after ICI are still being characterized, and it is unclear whether the clinical presentation, ancillary testing findings, and outcomes are different from spontaneous paraneoplastic neurological syndromes (PNS) involving the CNS [8,[10][11][12][13].…”

Section: Immune Checkpoint Inhibitor (Ici) Cancer Immunotherapy Enhan...mentioning

confidence: 99%

“…Some initial observations suggested that patients with neuroendocrine tumors (NET) and ICI‐triggered autoimmunity have worse outcomes but this was restricted in peripheral nervous system manifestations [11]. Similarly, a recent study showed that patients with post‐ICI antineuronal nuclear antibody (ANNA)‐1 or anti‐Hu neurological autoimmunity had worse neurological outcomes and higher mortality than spontaneous ANNA‐1 PNS [12].…”

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitor‐associated central nervous system autoimmunity

Valencia‐Sánchez

Sechi

Dubey

et al. 2023

Euro J of Neurology

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Background and purpose Outcome and rechallenge data on central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICIs) are limited. We aim to describe a large series of patients with ICI‐triggered CNS autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS). Methods We retrospectively reviewed Mayo Clinic patients with ICI‐triggered CNS autoimmunity (February 2015–June 2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]‐1 or anti‐Hu neurological autoimmunity, and/or neuroendocrine tumors [NET]) evaluated within the same period. Results Thirty‐one patients were included (55% female, median age = 63 years, range = 39–76). Median time from ICI initiation was 3.65 months (range = 0.8–44.5). The most common associated malignancies were melanoma and small cell lung cancer. CNS manifestations included encephalitis (n = 16), meningoencephalitis (n = 8), cerebellar ataxia (n = 4), demyelinating syndrome (n = 2), and myelopathy (n = 1). Magnetic resonance imaging was abnormal in 62%. Cerebrospinal fluid was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET (p = 0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow‐up (range = 0.7–46), 39% had unfavorable outcomes (grade ≥ 3). This was associated with higher severity degree at onset, shorter period from ICI to neurological symptom onset, and encephalitis. Four patients were rechallenged with ICI, and one relapsed. Patients with NET and with ANNA‐1 ICI‐triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts (p = 0.007 and p = 0.028, respectively). Conclusions One third of ICI‐related CNS autoimmunity patients have unfavorable outcomes. Relapses may occur after ICI rechallenge. Neural autoantibodies are often present, more commonly in patients with NET.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Immune Checkpoint Inhibitor (Ici) Cancer Immunotherapy Enhan...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitor‐associated central nervous system autoimmunity

Valencia‐Sánchez

Sechi

Dubey

et al. 2023

Euro J of Neurology

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“…Multiple reports have described the emergence of neurologic syndromes with ANNA1 (Hu) antibodies after immune checkpoint inhibitor therapy. 31…”

Section: Key Pointsmentioning

confidence: 99%

Paraneoplastic Neurologic Syndromes

Graber

2023

CONTINUUM: Lifelong Learning in Neurology

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OBJECTIVE Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. LATEST DEVELOPMENTS Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti–leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti–glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. ESSENTIAL POINTS All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.

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Autoimmune Movement Disorders Complicating Treatment with Immune Checkpoint Inhibitors

Dinoto,

Trentinaglia,

Carta

et al. 2024

Movement Disord Clin Pract

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BackgroundImmune checkpoint inhibitors (ICI) may trigger autoimmune neurological conditions, including movement disorders (MD).ObjectivesThe aim of this study was to characterize MDs occurring as immune‐related adverse events (irAEs) of ICIs.MethodsA systematic literature review of case reports/series of MDs as irAEs of ICIs was performed.ResultsOf 5682 eligible papers, 26 articles with 28 patients were included. MDs occur as a rare complication of cancer immunotherapy with heterogeneous clinical presentations and in most cases in association with other irAEs. Inflammatory basal ganglia T2/fluid attenuated inversion recovery abnormalities are rarely observed, but brain imaging is frequently unrevealing. Cerebrospinal fluid findings are frequently suggestive of inflammation. Half of cases are associated with a wide range of autoantibodies. Steroids and ICI withdrawal usually lead to improvement, even though some patients experienced relapses or a severe clinical course.ConclusionMDs are a rare complication of ICIs that should be promptly recognized to offer patients a correct diagnosis and treatment.

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Anti-Hu Antibodies in Patients With Neurologic Side Effects of Immune Checkpoint Inhibitors

Cited by 20 publications

References 40 publications

Immune checkpoint inhibitor‐associated central nervous system autoimmunity

Immune checkpoint inhibitor‐associated central nervous system autoimmunity

Paraneoplastic Neurologic Syndromes

Autoimmune Movement Disorders Complicating Treatment with Immune Checkpoint Inhibitors

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