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Current landscape and tailored management of immune-related adverse events.

ABSTRACT: Unprecedented advances have been made in immune checkpoint inhibitors (ICIs) in the treatment of cancer. However, the overall benefits from ICIs are impaired by the increasing incidence of immune-related adverse events (irAEs). Although several factors and mechanisms have been proposed in the development of irAEs, there is still incomprehensive understanding of irAEs. Therefore, it is urgent to identify certain risk factors and biomarkers that predict the development of irAEs, as well as to understand the underlying mechanisms of these adverse events. Herein, we comprehensively summarize the state-of-the-art knowledge about clinical features and the related risk factors of irAEs. Particularly, we also discuss relevant mechanisms of irAEs and address the mechanism-based strategies, aiming to develop a tailored management approach for irAEs.

SUBMITTER: Liu W

PROVIDER: S-EPMC10025325 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Current landscape and tailored management of immune-related adverse events.

Liu Wenhui W Luo Zhiying Z Liu Yiping Y Sun Bao B

Frontiers in pharmacology 20230306

Unprecedented advances have been made in immune checkpoint inhibitors (ICIs) in the treatment of cancer. However, the overall benefits from ICIs are impaired by the increasing incidence of immune-related adverse events (irAEs). Although several factors and mechanisms have been proposed in the development of irAEs, there is still incomprehensive understanding of irAEs. Therefore, it is urgent to identify certain risk factors and biomarkers that predict the development of irAEs, as well as to unde ...[more]

PMID: 36950013

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Project description:BackgroundManagement of immune-related adverse events (irAEs) is important as they cause treatment interruption or discontinuation, more often seen with combination immune checkpoint inhibitor (ICI) therapy. Here, we retrospectively evaluated the safety and effectiveness of anti-interleukin-6 receptor (anti-IL-6R) as therapy for irAEs.MethodsWe performed a retrospective multicenter study evaluating patients diagnosed with de novo irAEs or flare of pre-existing autoimmune disease following ICI and were treated with anti-IL-6R. Our objectives were to assess the improvement of irAEs as well as the overall tumor response rate (ORR) before and after anti-IL-6R treatment.ResultsWe identified a total of 92 patients who received therapeutic anti-IL-6R antibodies (tocilizumab or sarilumab). Median age was 61 years, 63% were men, 69% received anti-programmed cell death protein-1 (PD-1) antibodies alone, and 26% patients were treated with the combination of anti-cytotoxic T lymphocyte antigen-4 and anti-PD-1 antibodies. Cancer types were primarily melanoma (46%), genitourinary cancer (35%), and lung cancer (8%). Indications for using anti-IL-6R antibodies included inflammatory arthritis (73%), hepatitis/cholangitis (7%), myositis/myocarditis/myasthenia gravis (5%), polymyalgia rheumatica (4%), and one patient each with autoimmune scleroderma, nephritis, colitis, pneumonitis and central nervous system vasculitis. Notably, 88% of patients had received corticosteroids, and 36% received other disease-modifying antirheumatic drugs (DMARDs) as first-line therapies, but without adequate improvement. After initiation of anti-IL-6R (as first-line or post-corticosteroids and DMARDs), 73% of patients showed resolution or change to ≤grade 1 of irAEs after a median of 2.0 months from initiation of anti-IL-6R therapy. Six patients (7%) stopped anti-IL-6R due to adverse events. Of 70 evaluable patients by RECIST (Response Evaluation Criteria in Solid Tumors) V.1.1 criteria; the ORR was 66% prior versus 66% after anti-IL-6R (95% CI, 54% to 77%), with 8% higher complete response rate. Of 34 evaluable patients with melanoma, the ORR was 56% prior and increased to 68% after anti-IL-6R (p=0.04).ConclusionTargeting IL-6R could be an effective approach to treat several irAE types without hindering antitumor immunity. This study supports ongoing clinical trials evaluating the safety and efficacy of tocilizumab (anti-IL-6R antibody) in combination with ICIs (NCT04940299, NCT03999749).

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Current landscape and tailored management of immune-related adverse events.

Publications

Current landscape and tailored management of immune-related adverse events.

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