Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy

Jing, Ying; Liu, Jin; Ye, Youqiong; Pan, Lei; Deng, Hui; Wang, Yushu; Yang, Yang; Diao, Lixia; Lin, Steven H.; Mills, Gordon B.; Zhuang, Guanglei; Xue, Xinying; Han, Leng

doi:10.1038/s41467-020-18742-9

Cited by 144 publications

(135 citation statements)

References 38 publications

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“…It is suggested that T cell receptor (TCR) diversity, CD8 + T cell clonal expansion and tumor mutation burden (TMB) may potentially predict irAE, although this is based on a single factor or under limited circumstances. Therefore, there is a lack of comprehensive methods to identify irAE biomarkers (12). The main aspects of irAE management include toxicity identification and classification, immunosuppression, and personalized modification of ICI management.…”

Section: Discussionmentioning

confidence: 99%

Delayed thrombocytopenia as a rare but serious adverse event secondary to immune checkpoint inhibitor: a case report

Zhou¹,

Li²,

Tang³

et al. 2021

Ann Palliat Med

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Immune checkpoint inhibitors (ICIs) are a recent breakthrough in antitumor drugs, although their overall safety has not been fully defined. Compared to conventional chemotherapy, ICIs exhibit different patterns of immunotoxicity, and immune-related adverse events (irAEs) have an immunological basis that is more toxic than usual and have a broad spectrum of manifestations involving different organ systems. Early recognition of symptoms and timely intervention are very important in managing immunerelated adverse events (irAEs). In this study, we report a case of delayed immune thrombocytopenia in a patient treated with nivolumab for small cell lung cancer (SCLC). We found that thrombocytopenia was associated with the presence of platelet antibodies, autoantibodies, and thyroglobulin antibodies, accompanied by a decrease in the number of helper T cells and regulatory T cells. Platelets returned to normal after the removal of antibodies by plasma exchanges and methylprednisolone. We hypothesized that thrombocytopenia in patients was an antibody-driven and T-cell-mediated process. Although these observations indirectly suggest that cytokine changes contribute to immune dysregulation during irAE, prospective validation is needed to explain the confounding etiologies that may contribute to cytokine dysregulation. Therefore, studying the relationship between T cell subpopulations, cytokines and irAE in a larger population may be crucial for identifying biomarkers for ICI.

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Section: Discussionmentioning

confidence: 99%

Delayed thrombocytopenia as a rare but serious adverse event secondary to immune checkpoint inhibitor: a case report

Zhou¹,

Li²,

Tang³

et al. 2021

Ann Palliat Med

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“…26 Recently, Jing et al reported that the combination of lymphocyte cytosolic protein 1 and adenosine diphosphate dependent glucokinase is a promising biomarker for irAEs. 27 However, biomarkers for predicting early-and late-onset CIP have not been reported.…”

Section: Discussionmentioning

confidence: 99%

Radiographic Features and Prognosis of Early- and Late-onset Non-small Cell Lung Cancer Immune Checkpoint Inhibitor-related Pneumonitis

Huang

Zang

et al. 2021

Preprint

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Background: Immunotherapy is becoming a standard of care for non-small cell lung cancer (NSCLC). Checkpoint inhibitor-associated pneumonia (CIP) is a rare and potentially life-threatening event that can occur at any time during tumor immunotherapy. However, there may be differences in the radiological patterns and prognosis of CIP during different periods. This study aimed to investigate the radiographic features and prognosis of early- and late-onset immune-related pneumonitis. Methods: We retrospectively analyzed the clinical data of 677 NSCLC patients receiving immunotherapy to identify 32 patients with CIP who were being effectively treated by hormonotherapy, analyzed the clinical and radiographic data, and summarized the radiological features and prognosis of early- and late-onset CIP. Results: CIP had an incidence of 4.7%, a median onset time of 2.4 months, and a mortality of 28.1%. Among these, CIP included 14 early-onset cases, where grade ≥3 CIP accounted for 92.9%, main radiographic pattern was organizing pneumonia (OP)-like pattern, and mortality was 50.0%. We also identified 18 late-onset CIPs, where grade ≥3 CIP accounted for 50.0%, main radiographic pattern was nonspecific interstitial pneumonia (NSIP)-like pattern, and mortality was 11.1%. The overall survival rate of the early-onset group was significantly lower than that of the late-onset group (P < 0.05).Conclusion: Early-onset CIP cases were higher in the National Comprehensive Cancer Network (NCCN) grade and mainly presented with an OP-like radiographic pattern; whereas, late-onset CIP cases were lower in NCCN grade and mainly presented with an NSIP-like radiographic pattern. Finally, the prognosis of the early-onset CIP group was poorer than that of the late-onset CIP group. We believe that this study will be helpful for clinicians for making early diagnosis and deciding treatment modalities for patients with CIP.

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“…Recent studies have also used data sources beyond clinical trial data, such as patient studies and pharmacovigilance data combined with omics data, to identify intestinal microbiome profiles, tumor immune biomarkers, and differential gene expression associated with elevated irAE risk. [18][19][20] Barriers to aggregating irAE clinical trial data Clinical investigators face several challenges related to nomenclature and definitions of toxicity in capturing the characteristics and severity of irAEs. In general, the goldstandard mechanism that can definitively diagnose irAEs, and thus confirm that the toxicity is due to ICI treatment, and not a combination treatment partner such as chemotherapy or an alternative diagnosis, is biopsy with histopathological evidence of inflammation.…”

Section: Improving Clinical Trial Data Reporting: Standardizing Ae Terminology and Case Report Forms Would Facilitate Pooled Analyses Of mentioning

confidence: 99%

Immune-related adverse events associated with immune checkpoint inhibitors: a call to action for collecting and sharing clinical trial and real-world data

Reynolds

Arora

Elayavilli³

et al. 2021

J Immunother Cancer

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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer, improving outcomes in patients with advanced malignancies. The use of ICIs in clinical practice, and the number of ICI clinical trials, are rapidly increasing. The use of ICIs in combination with other forms of cancer therapy, such as chemotherapy, radiotherapy, or targeted therapy, is also expanding. However, immune-related adverse events (irAEs) can be serious in up to a third of patients. Critical questions remain surrounding the characteristics and outcomes of irAEs, and how they may affect the overall risk–benefit relationship for combination therapies. This article proposes a framework for irAE classification and reporting, and identifies limitations in the capture and sharing of data on irAEs from current clinical trial and real-world data. We outline key gaps and suggestions for clinicians, clinical investigators, drug sponsors, patients, and other stakeholders to make these critical data more available to researchers for pooled analysis, to advance contemporary understanding of irAEs, and ultimately improve the efficacy of ICIs.

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Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy

Cited by 144 publications

References 38 publications

Delayed thrombocytopenia as a rare but serious adverse event secondary to immune checkpoint inhibitor: a case report

Delayed thrombocytopenia as a rare but serious adverse event secondary to immune checkpoint inhibitor: a case report

Radiographic Features and Prognosis of Early- and Late-onset Non-small Cell Lung Cancer Immune Checkpoint Inhibitor-related Pneumonitis

Immune-related adverse events associated with immune checkpoint inhibitors: a call to action for collecting and sharing clinical trial and real-world data

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