Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls

Darnell, Eli P.; Mooradian, Meghan J.; Baruch, Erez N.; Yilmaz, Melis; Reynolds, Kerry L.

doi:10.1007/s11912-020-0897-9

Cited by 242 publications

(225 citation statements)

References 51 publications

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“…In mild cases the symptoms might disappear by its own or after termination of CPI exposure, but severe irAEs needs to be managed with immune-modulatory medications, such as steroids, biological therapy, or cytostatic drugs [ 108 , 109 , 110 ]. In addition, the characteristic ASIA symptoms can occur in patients who have developed musculoskeletal toxicities, which are found in 2–12% of cases and can manifest as inflammatory arthritis, myalgia, myositis, and syndromes similar to polymyalgia [ 111 ]. Fever is a common complication of immunotherapy.…”

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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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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“…As a consequence of the rapid extension of therapeutic indications in different tumor types (the agnostic approval of pembrolizumab is a paradigmatic example) and settings, clinicians are increasingly facing both common and rare irAEs, which can virtually affect any organ or system in the body, requiring new skills to timely diagnosis, and a multidisciplinary approach to successful patient management [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

et al. 2020

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The advent of immune checkpoint inhibitors (ICIs) caused a paradigm shift both in drug development and clinical practice; however, by virtue of their mechanism of action, the excessively activated immune system results in a multitude of offtarget toxicities, the so-called immune-related adverse events (irAEs), requiring new skills for timely diagnosis and a multidisciplinary approach to successfully manage the patients. In the recent past, a plethora of large-scale pharmacovigilance analyses have characterized various irAEs in terms of spectrum and clinical features in the real world. This review aims to summarize and critically appraise the current landscape of pharmacovigilance studies, thus deriving take-home messages for oncologists. A brief primer to study design, conduction, and data interpretation is also offered. As of February 2020, 30 real-world postmarketing studies have characterized multiple irAEs through international spontaneous reporting systems, namely WHO Vigibase and the US FDA Adverse Event Reporting System. The majority of studies investigated a single irAE and provided new epidemiological evidence about class-specific patterns of irAEs (i.e. anti-cytotoxic T-lymphocyte antigen 4 [CTLA-4] versus anti-programmed cell death 1 [PD-1] receptor, and its ligand [PD-L1]), kinetics of appearance, co-occurrences (overlap) among irAEs, and fatality rate. Oncologists should be aware of both strengths and limitations of these pharmacovigilance analyses, especially in terms of data interpretation. Optimal management (including rechallenge), predictivity of irAEs (as potential biomarkers of effectiveness), and comparative safety of ICIs (also in terms of combination regimens) represent key research priorities for next-generation real-world studies.

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“…Although immunotherapy is a targeted therapy and therefore it is better tolerated compared to common chemotherapy, it has been associated with the emergence of a new panel of dysimmune toxicities called irAEs [9,[118][119][120].…”

Section: Immune-related Adverse Events To Immunotherapymentioning

confidence: 99%

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

Ralli

Botticelli

Visconti

et al. 2020

Journal of Immunology Research

151

138

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Melanoma is one of the most immunologic malignancies based on its higher prevalence in immune-compromised patients, the evidence of brisk lymphocytic infiltrates in both primary tumors and metastases, the documented recognition of melanoma antigens by tumor-infiltrating T lymphocytes and, most important, evidence that melanoma responds to immunotherapy. The use of immunotherapy in the treatment of metastatic melanoma is a relatively late discovery for this malignancy. Recent studies have shown a significantly higher success rate with combination of immunotherapy and chemotherapy, radiotherapy, or targeted molecular therapy. Immunotherapy is associated to a panel of dysimmune toxicities called immune-related adverse events that can affect one or more organs and may limit its use. Future directions in the treatment of metastatic melanoma include immunotherapy with anti-PD1 antibodies or targeted therapy with BRAF and MEK inhibitors.

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Immune-Related Adverse Events (irAEs): Diagnosis, Management, and Clinical Pearls

Cited by 242 publications

References 51 publications

Classical Examples of the Concept of the ASIA Syndrome

Classical Examples of the Concept of the ASIA Syndrome

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance

Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions

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