Immunogenetic variations predict immune-related adverse events for PD-1/PD-L1 inhibitors

Xin, Zhaodan; You, Lei; Na, Feifei; Li, Jin; Chen, Min; Song, Jiajia; Bai, Ling; Chen, Jie; Zhou, Juan; Ying, Binwu

doi:10.1016/j.ejca.2023.01.034

Cited by 10 publications

(9 citation statements)

References 47 publications

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“…IFNW1 (rs10964859), IFNL4 (rs12979860), PD-L1 (rs4143815), and CTLA-4 (rs3087243, rs11571302, and r27565213) SNPs were associated with increased grade ≥3 irAEs, while UNG (rs246079) SNP was associated with reduced irAEs [ 72 ]. A study by Xin et al screened 340 patients for 37 SNPs and revealed increased irAEs in MAPK1 (rs3810610) and ADAD1 (rs17388568), and decreased irAEs were observed in PTPRC (rs6428474) and IL6 (rs1800796) SNPs [ 74 ]. A multiplex genotyping in 89 patients with melanoma revealed 12 deleterious and 18 protective SNP variants for irAEs.…”

Section: Biomarkersmentioning

confidence: 99%

“…Anti-BP180 IgG was associated with dermatologic irAEs, but not all irAEs, from anti-PD1/PD-L1 in NSCLC [ 110 ]. Other potential biomarkers include the MAPK1 SNP (rs3810610), which was found to be a risk factor for dermatologic irAEs from a screening of 39 SNPs in 340 patients with solid tumors [ 74 ]. Another study by Ali et al established an association between the HLA-DRB1*11:01 allele with pruritus from ICIs in malignant melanoma and NSCLC (OR 4.53, p = 0.0021) [ 111 ].…”

Section: Biomarkersmentioning

confidence: 99%

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Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

Ponvilawan,

Khan,

Subramanian

et al. 2024

Cancers

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Immune-related adverse events (irAEs) are the most common complication of immune checkpoint inhibitor (ICI) therapy. With the widespread use of ICIs in patients with solid tumors, up to 40% of the patients develop irAEs within five months of treatment, and 11% develop severe irAEs requiring interventions. A predictive test for irAEs would be a crucial tool for monitoring for complications during and after ICI therapy. We performed an extensive review of potential predictive biomarkers for irAEs in patients who received ICI therapy. Currently, only thyroid-stimulating hormone is utilized in common clinical practice. This is due to the unavailability of commercial tests and unclear predictive values from various studies. Given the lack of single strong predictive biomarkers, some novel approaches using composite scores using genomic, transcriptomics, cytokine levels, or clinical parameters appear appealing. Still, these have yet to be validated and incorporated into clinical practice. Further research conducted to validate the models before implementing them into real-world settings will be of the utmost importance for irAE prediction.

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Section: Biomarkersmentioning

confidence: 99%

Section: Biomarkersmentioning

confidence: 99%

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

Ponvilawan,

Khan,

Subramanian

et al. 2024

Cancers

View full text Add to dashboard Cite

show abstract

“…47 These reports emphasize the urgency of identifying tools that assess the risk and severity of developing irAE and their implications for patient outcomes before starting treatment. In this regard, Xin et al 48 identified polymorphisms associated with irAEs and irAEs-free survival in PD-1/PD-L1 blockade-treated patients with different types of cancer, but only two patients had HCC in that cohort. Thus, the ability to identify early predictors of AE development is still a mandatory task in the field of liver cancer.…”

Section: Variable Patient Outcomementioning

confidence: 99%

“…In this regard, Xin et al. 48 identified polymorphisms associated with irAEs and irAEs‐free survival in PD‐1/PD‐L1 blockade‐treated patients with different types of cancer, but only two patients had HCC in that cohort. Thus, the ability to identify early predictors of AE development is still a mandatory task in the field of liver cancer.…”

Section: Swot Analysis Of Systemic Treatment In Hcc Fieldmentioning

confidence: 99%

Systemic therapies in hepatocellular carcinoma: A revolution?

Fortuny,

Sanduzzi‐Zamparelli,

Reig

2024

UEG Journal

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The evolution in systemic therapies in hepatocellular carcinoma (HCC) signifies a strategy of high‐cost, high‐gain innovation that originated with sorafenib, despite its limited impact on tumor response. This strategic approach paved the way for the emergence of a second wave of the short‐lived competitive advantage, exemplified by the incorporation of atezolizumab plus bevacizumab and tremelimumab plus durvalumab. In the context of safety concerns within the liver cancer domain, the IMBRAVE150 and HIMALAYA trials boldly incorporated bevacizumab and tremelimumab, respectively, demonstrating the continuation of the high‐risk, high‐reward innovation paradigm. This review delves into the strengths, weaknesses, opportunities, and threats analysis of systemic therapies in the field of HCC.

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“…Notably, more than two-thirds of documented cases are irAEs, with three specific drugs (ipilimumab, nivolumab, and pembrolizumab) accounting for nearly 60% of these incidents [14]. The severity of these toxicities varies from mild to life-threatening, creating a clinical dilemma regarding whether to discontinue treatment or manage the condition through frequent hospitalization and immunosuppressive therapy [16][17][18]. In this review, we mainly discuss the irAEs and predictive biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers

Miao,

Quan,

Tang

et al. 2024

Int. J. Biol. Sci.

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Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types of cancer. However, the widespread use of ICIs has brought about a number of safety concerns, especially the development of immune-related adverse events (irAEs). These serious complications could result in treatment discontinuation and even life-threatening consequences, making it critical to identify high-risk groups and predictive markers of irAEs before initiating therapy. To this end, the current article examines several potential predictive markers of irAEs in important organs affected by ICIs. While retrospective studies have yielded some promising results, limitations such as small sample sizes, variable patient populations, and specific cancer types and ICIs studied make it difficult to generalize the findings. Therefore, prospective cohort studies and real-world investigations are needed to validate the potential of different biomarkers in predicting irAEs risk. Overall, identifying predictive markers of irAEs is a crucial step towards improving patient safety and enhancing the management of irAEs. With ongoing research efforts, it is hoped that more accurate and reliable biomarkers will be identified and incorporated into clinical practice to guide treatment decisions and prevent the development of irAEs in susceptible patients.

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Immunogenetic variations predict immune-related adverse events for PD-1/PD-L1 inhibitors

Cited by 10 publications

References 47 publications

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors

Systemic therapies in hepatocellular carcinoma: A revolution?

Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers

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