Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer

Issa, Majd; Tang, Joy; Guo, Yizhen; Coss, Christopher C.; Mace, Thomas A.; Bischof, Jason J.; Phelps, Mitch A.; Presley, Carolyn J.; Owen, Dwight H.

doi:10.1080/14737140.2022.2094772

Cited by 9 publications

(11 citation statements)

References 192 publications

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“…Genetic factors are likely to be important modifiers of risk, but studies exploring genetic predisposition to developing irAE have reported variable findings. Despite an association between human leukocyte antigen profiles and autoimmunity, no clear association has yet been identified between human leukocyte antigen profile and irAE risk 26 . In an exploratory study of a small number of patients with melanoma, single nucleotide polymorphisms were identified which conferred either increased or decreased risk for irAE, but larger studies are required to confirm the significance of these findings 27 …”

Section: Risk Factors For Iraementioning

confidence: 99%

“…Despite an association between human leukocyte antigen profiles and autoimmunity, no clear association has yet been identified between human leukocyte antigen profile and irAE risk. [26] In an exploratory study of a small number of patients with melanoma, single nucleotide polymorphisms were identified which conferred either increased or decreased risk for irAE, but larger studies are required to confirm the significance of these findings. [27] Presence of metastatic disease to the liver was hypothesized to be a potential risk for hepatotoxicity, [28] although this has not been borne out in real-world studies.…”

Section: Risk Factors For Iraementioning

confidence: 99%

“…Despite extensive exploration of patient, cancer, and treatment-specific variables, few definitive risk factors for development of irAE have been identified. [26] The only patient-specific risk to have been reproducibly identified so far is preexisting autoimmune disease. Patients with autoimmune disease were excluded from clinical trials, but accumulating evidence from case series and retrospective real-world studies suggests a higher risk for development of de novo irAE in these patients.…”

Section: Risk Factors For Iraementioning

confidence: 99%

“…Patients with autoimmune disease were excluded from clinical trials, but accumulating evidence from case series and retrospective real-world studies suggests a higher risk for development of de novo irAE in these patients. [26] Genetic factors are likely to be important modifiers of risk, but studies exploring genetic predisposition to developing irAE have reported variable findings. Despite an association between human leukocyte antigen profiles and autoimmunity, no clear association has yet been identified between human leukocyte antigen profile and irAE risk.…”

Section: Risk Factors For Iraementioning

confidence: 99%

“…Despite extensive exploration of patient, cancer, and treatment-specific variables, few definitive risk factors for development of irAE have been identified 26 . The only patient-specific risk to have been reproducibly identified so far is preexisting autoimmune disease.…”

Section: Risk Factors For Iraementioning

confidence: 99%

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Checkpoint inhibitor hepatotoxicity: pathogenesis and management

2023

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Immunotherapy, including immune checkpoint inhibitor (ICI) therapy, has been a paradigm shift in cancer therapeutics, producing durable cancer responses across a range of primary malignancies. ICI drugs increase immune activity against tumor cells, but may also reduce immune tolerance to self-antigens, resulting in immune-mediated tissue damage. ICI-associated hepatotoxicity usually manifests as hepatocellular enzyme elevation and may occur in 2%-25% of ICI-treated patients. Although ICI-associated hepatotoxicity is clinically and pathologically distinct from idiopathic autoimmune hepatitis, our understanding of its pathogenesis continues to evolve. Pending greater understanding of the pathophysiology, mainstay of management remains through treatment with high-dose corticosteroids. This approach works for many patients, but up to 30% of patients with high-grade hepatotoxicity may not respond to corticosteroids alone. Furthermore, atypical cholestatic presentations are increasingly recognized, and rare cases of fulminant hepatitis due to ICI hepatotoxicity have been reported. Optimal management for these challenging patients remains uncertain. Herein, we review the current understanding of pathogenesis of ICI-associated toxicities, with a focus on hepatotoxicity. Based on the existing literature, we propose evolving management approaches to incorporate strategies to limit excess corticosteroid exposure, and address rare but important presentations of cholestatic hepatitis and fulminant liver failure. Finally, as ICI hepatotoxicity frequently occurs in the context of treatment for advanced malignancy, we review the impact of hepatotoxicity and its treatment on cancer outcomes, and the overall safety of re-challenge with ICI, for patients who may have limited treatment options.

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Section: Risk Factors For Iraementioning

confidence: 99%

Section: Risk Factors For Iraementioning

confidence: 99%

Section: Risk Factors For Iraementioning

confidence: 99%

Section: Risk Factors For Iraementioning

confidence: 99%

Section: Risk Factors For Iraementioning

confidence: 99%

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Checkpoint inhibitor hepatotoxicity: pathogenesis and management

2023

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Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Likhitsup,

Fontana

2024

Current Opinion in Gastroenterology

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Purpose of review The aim is to summarize the latest data on the incidence, clinical manifestations, and management of immune- mediated liver injury from checkpoint inhibitors (ILICI). Recent findings ILICI develops in 10–15% of oncology patients receiving immunotherapy with most having asymptomatic serum aminotransferase and/or alkaline phosphatase elevations. Most grade 1–2 ILICI patients improve with drug discontinuation and/or short-term oral corticosteroids. In contrast, the 2–3% with grade 3/4 hepatotoxicity frequently require oral or intravenous corticosteroids and some are hospitalized to initiate further immunosuppression with mycophenolate mofetil or azathioprine. Liver biopsy is generally reserved for patients with atypical features or those with severe hepatotoxicity who fail to respond to treatment. Up to 3% of ILICI patients with a cholestatic profile have MRI evidence of intra or extrahepatic cholangitis that responds poorly to immunosuppression. Most ILICI patients improve during follow-up and liver-related death is very uncommon (<1%). Up to 30% of rechallenged ILICI patients develop recurrent hepatotoxicity with a shorter latency. Summary ILICI is increasingly encountered by gastroenterologists evaluating oncology patients with abnormal liver biochemistries. A stepwise approach to exclude viral hepatitis, alcohol, hepatic metastases, and pancreaticobiliary disease is recommended. The majority of ILICI patients fully recover with ICI discontinuation and short-term corticosteroids or a second line immunosuppressant.

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Prospective Clinical Trials to Advance the Study of Immunotherapy Toxicities

Cluxton¹,

Naidoo²

2023

Preprint

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Immune checkpoint inhibitors (ICIs) are a class of drug that produces durable and sustained anti-tumour responses in a wide variety of malignancies. The exponential rise in their use has been mirrored by a rise in immune-related adverse events (irAEs). Knowledge of such toxicities, as well as effective management algorithms for these toxicities, is essential to optimize clinical efficacy and safety. Currently, the guidelines for management of the irAEs are based largely on retrospective studies and case series. In this article, we review the current landscape of clinical trials investigating the management of irAEs with an aim to develop standardized, randomized controlled trial-based management algorithms for ICI-related toxicities.

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Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer

Cited by 9 publications

References 192 publications

Checkpoint inhibitor hepatotoxicity: pathogenesis and management

Checkpoint inhibitor hepatotoxicity: pathogenesis and management

Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

Prospective Clinical Trials to Advance the Study of Immunotherapy Toxicities

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