CNS Side Effects of Immune Checkpoint Inhibitors: Preclinical Models, Genetics and Multimodality Therapy

McGinnis, Gwendolyn J.; Raber, Jacob

doi:10.2217/imt-2017-0056

Cited by 36 publications

(18 citation statements)

References 104 publications

(63 reference statements)

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“…Our results suggest that the occurrence of neurotoxicity and neuroendocrinological irAEs could potentially have long-term neuropsychiatric and neurovegetative consequences in humans. This suggestion is consistent with the complex interactions between stress, the immune system, the central nervous system, and the tumor microenvironment described previously in preclinical models [32] [33] [34].…”

Section: Discussionsupporting

confidence: 92%

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab

Rogiers

Leys

Lauwyck

et al. 2020

Journal of Immunology Research

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Purpose. To assess neurocognitive function (NCF), psychosocial outcome, health-related quality of life (HRQoL), and long-term effects of immune-related adverse events (irAE) on metastatic melanoma survivors treated with ipilimumab (IPI). Methods. Melanoma survivors were identified within two study populations (N=104), at a single-center university hospital, and defined as patients who were disease-free for at least 2 years after initiating IPI. Data were collected using 4 patient-reported outcome measures, computerized NCF testing, and a semistructured interview at the start and 1-year follow-up. Results. Out of 18 eligible survivors, 17 were recruited (5F/12M); median age is 57 years (range 33-86); and median time since initiating IPI was 5.6 years (range 2.1-9.3). The clinical interview revealed that survivors suffered from cancer-related emotional distress such as fear of recurrence (N=8), existential problems (N=2), survivor guilt (N=2), and posttraumatic stress disorder (N=6). The mean EORTC QLQ-C30 Global Score was not significantly different from the European mean of the healthy population. Nine survivors reported anxiety and/or depression (Hospitalization Depression Scale) during the survey. Seven survivors (41%) reported fatigue (Fatigue Severity Scale). Seven patients (41%) had impairment in NCF; only three out of seven survivors had impairment in subjective cognition (Cognitive Failure Questionnaire). Anxiety, depression, fatigue, and neurocognitive symptoms remained stable at the 1-year follow-up. All cases of skin toxicity (N=8), hepatitis (N=1), colitis (N=3), and sarcoidosis (N=1) resolved without impact on HRQoL. Three survivors experienced hypophysitis; all suffered from persistent fatigue and cognitive complaints 5 years after onset. One survivor who experienced a Guillain-Barré-like syndrome suffered from persisting depression, fatigue, and impairment in NCF. Conclusion. A majority of melanoma survivors treated with IPI continue to suffer from emotional distress and impairment in NCF. Timely detection in order to offer tailored care is imperative, with special attention for survivors with a history of neuroendocrine or neurological irAE. The trial is registered with B.U.N. 143201421920.

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Section: Discussionsupporting

confidence: 92%

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab

Rogiers

Leys

Lauwyck

et al. 2020

Journal of Immunology Research

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“…However, cancer-related cognitive impairment (CRCI) is frequently reported and seems to be associated with cancer and all components of cancer treatment [41]. Despite the fact that there is limited research describing the effects of ICI on the brain, given the highly regulated immune response in the brain, it is expected that all the treatment modalities and cancer itself might be associated with CRCI [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

Health-related quality of life of long-term advanced melanoma survivors treated with anti-CTLA-4 immune checkpoint inhibition compared to matched controls

et al. 2020

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“…In patients with non-small cell lung cancer, fever was associated with a low level of progression free survival [ 112 ]. Chronic fatigue, not-restful sleep, sleep disturbances, cognitive alterations, memory loss occur in up to 42% of cases and may be associated with immune activation in the central nervous system [ 113 ]. It should not be forgotten that the described symptoms can be a manifestation of endocrine abnormalities [ 114 ].…”

Section: Classical Examples Of the Asia Syndromementioning

confidence: 99%

Classical Examples of the Concept of the ASIA Syndrome

et al. 2020

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Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.

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CNS Side Effects of Immune Checkpoint Inhibitors: Preclinical Models, Genetics and Multimodality Therapy

Cited by 36 publications

References 104 publications

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab

Neurocognitive Function, Psychosocial Outcome, and Health-Related Quality of Life of the First-Generation Metastatic Melanoma Survivors Treated with Ipilimumab

Health-related quality of life of long-term advanced melanoma survivors treated with anti-CTLA-4 immune checkpoint inhibition compared to matched controls

Classical Examples of the Concept of the ASIA Syndrome

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