Diagnosis and Management of Immune Related Adverse Events (irAEs) in Cancer Immunotherapy

Liu, Yihe; Zang, Xin-Yuan; Wang, Jincheng; Huang, Shanshan; Jiang, Xu; Zhang, Peng

doi:10.1016/j.biopha.2019.109437

Cited by 60 publications

(53 citation statements)

References 66 publications

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“…Similarly, immune dysregulation is the basis of the immunotherapy toxicities. Increasing levels of cytokines and infiltration of T-cell on normal tissues are described as two possible mechanisms underlying the immune-related adverse events [41,42]. High levels of inflammatory cytokines have been associated with prediction and severity of toxicity in patients receiving anti-PD-1-based immunotherapy [43].…”

Section: Potential Interactions Between Sars-cov-2 and Icismentioning

confidence: 99%

COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis, potential interactions, and management

Russano

Citarella

Napolitano

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: The COVID-19 pandemic occurred amid the cancer immunotherapy revolution. Immune checkpoint inhibitors (ICIs) have become the standard of care for several solid cancers and are associated with peculiar toxicities, including pneumonitis which has similar features to COVID-19 pneumonia. Areas covered: We summarize the main hallmarks of lung injury induced by ICIs and severe acute respiratory syndrome coronavirus 2 and discuss the critical aspects for differential diagnosis and management. Symptoms and radiological findings are often similar; conversely, treatments are quite different. Furthermore, we focus on potential interactions generating hypotheses that need confirmatory studies. Expert opinion: All cancer patients treated with immunotherapy should receive screening for SARS-CoV-2. This would improve the diagnosis and management of pneumonia and guide therapeutic choices. Furthermore, clinicians could estimate the risk/benefit of continuing ICI treatment in COVID-19 positive patients. Temporary withdrawal of the immunotherapy treatment pending resolution of viral infection may be a reasonable option in long-responders patients.

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Section: Potential Interactions Between Sars-cov-2 and Icismentioning

confidence: 99%

COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis, potential interactions, and management

Russano

Citarella

Napolitano

et al. 2020

Expert Opinion on Biological Therapy

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“…According to the National Cancer Institute's Common Terminology Criteria, irAEs of the lower gastro-intestinal tract may present as mild-to-moderate transient diarrhea (grade 1) to life-threatening consequences with urgent intervention indicated (grade 4) or death (grade 5) 1 . ICPI-induced diarrhea occurs in up to 30% of patients in clinical trials [3].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, mechanisms underlying development of gut inflammation and colitis in a subgroup of patients on ICPIs therapy still remain quite unclear [3]. However, it has been widely shown that gut bacteria represent fundamental mediators of ICPIs toxicity by dysregulation of gastro-intestinal mucosal immunity and persistent T-cell activation, thus resulting in a pro-inflammatory state and occurrence of autoimmune-type manifestations [1].…”

Section: Discussionmentioning

confidence: 99%

Collagenous colitis and atezolizumab therapy: an atypical case

Gallo

Talerico

Novello

et al. 2020

Clin J Gastroenterol

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Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti-PD-1 (programmed cell death protein 1), and PD-L1 (programmed cell death protein-ligand 1) are emerging drugs that have radically changed treatment and prognosis of different types of tumors. However, despite their considerable benefits, immune checkpoint inhibitors are associated with numerous side effects involving several organs. Gastrointestinal toxicities represent some of these most common adverse events. While clinical presentation usually ranges from mild diarrhea to life-threatening colitis, typical endoscopic and histologic findings of immune-mediated colitis often resemble those of inflammatory bowel diseases. However, less common patterns are lymphocytic colitis and, rarely, collagenous colitis. Physician and pathologists must be aware of the wide spectrum of clinical and histological findings that may be encountered in immune-related gastro-intestinal toxicities. We report a rare and atypical case of collagenous colitis occurred in a woman affected by stage IV lung adenocarcinoma, on atezolizumab therapy.

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“…In general, for targeted therapy and for the most studied ICPi in particular, there is a wide variability from the first drug administration to irAE onset. IrAE may occur at any time and target multiple tissues, but generally cutaneous manifestations frequently appear in the first 2 weeks; then gastrointestinal side effects develop, usually within 6 weeks, followed by endocrine involvement (7-10 weeks) and respiratory system toxicity (8-14 weeks) [10]. However, very late reactions, even 1 year after stopping the treatment, may appear.…”

Section: Discussionmentioning

confidence: 99%

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature

et al. 2020

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Introduction In the last years, many new drugs have been developed targeting different oncology pathways, overall improving both quality of life and survival in several malignancies. However, the increase of those therapies is associated with novel toxicities, mainly immune-related adverse events (irAEs), never observed before. Different irAEs are now well characterized, and, among them, neuromuscular complications, following immune checkpoint inhibitor (ICPi) therapy, are increasingly studied and described. However, there are also neurological complications related to the use of other targeted therapies, less known and probably underestimated. Herein we describe two oncological patients who developed neuromuscular diseases after administration of targeted therapies, different from ICPi. Case reports The first patient was treated with the combination of Vemurafenib and Cobimetinib, BRAF and MEK inhibitors, respectively, for a cutaneous melanoma. One year after the beginning of the combined treatment, she developed a sub-acute motor neuropathy with predominant cranial nerve involvement. She was successfully treated with methylprednisolone. The second patient received therapy with Imatinib, tyrosine kinase inhibitor and precursor of the targeted therapy, for a gastrointestinal stromal tumour. Few days after the first administration, he developed generalized myasthenia gravis with respiratory failure. Clinical remission was obtained with plasma-exchange, intravenous immunoglobulins and steroids. Discussion and Conclusion We strengthen the relevance of neuromuscular complications which may occur long after treatment start or in patients receiving not only the latest ICPi but also "older" and apparently better-known targeted therapies. Also in the latter cases, an immune-mediated "off-target" pathogenic mechanism can be hypothesized, and consequences can be life threatening, if not promptly diagnosed and appropriately managed.

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Diagnosis and Management of Immune Related Adverse Events (irAEs) in Cancer Immunotherapy

Cited by 60 publications

References 66 publications

COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis, potential interactions, and management

COVID-19 pneumonia and immune-related pneumonitis: critical issues on differential diagnosis, potential interactions, and management

Collagenous colitis and atezolizumab therapy: an atypical case

Neuromuscular complications following targeted therapy in cancer patients: beyond the immune checkpoint inhibitors. Case reports and review of the literature

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