Evaluation of serum IL-17 levels during ipilimumab therapy: Correlation with colitis.

Callahan, Margaret K.; Yang, Aili; Tandon, S; Xu, Ya Ming; Subudhi, Sumit K.; Roman, Ruth-Ann; Heine, Agnes I.; Pogoriler, E.; Kuk, Deborah; Panageas, K.; Yuan, Jiong; Allison, James P.; Wolchok, J. D.

doi:10.1200/jco.2011.29.15_suppl.2505

Cited by 109 publications

(69 citation statements)

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“…This finding could contribute not only to predicting the outcome of patients treated with ipilimumab but also the occurrence of irAE. Additional preliminary studies have noted a correlation between serum IL-17 levels, Th17 cells, and symptomatic colitis (48). The latter finding suggests a possible specific means to address the toxicity using neutralizing IL-117 antibodies.…”

Section: Ipilimumab and Possible Predictive Markersmentioning

confidence: 90%

Biomarkers for Immunostimulatory Monoclonal Antibodies in Combination Strategies for Melanoma and Other Tumor Types

Ascierto

Kalos

Schaer

et al. 2013

Clinical Cancer Research

130

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Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising new approach of immunotherapy for cancer. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. Ipilimumab was the first treatment to ever show enhanced overall survival (OS) for patients with stage IV melanoma. However, measuring response rates using standard Response Evaluation Criteria in Solid Tumors (RECIST) or modified World Health Organization criteria or progression-free survival does not accurately capture the potential for clinical benefit for ipilimumab-treated patients. As immunotherapy approaches are translated into more tumor types, it is important to study biomarkers, which may be more predictive of OS to identify the patients most likely to have clinical benefit. Ipilimumab is the first-in-class of a series of immunomodulating antibodies that are in clinical development. Anti-PD1 (nivolumab and MK-3475), anti-PD-L1 (BMS-936 559, RG7446, and MEDI4736), anti-CD137 (urelumab), anti-OX40, anti-GITR, and anti-CD40 monoclonal antibodies are just some of the agents that are being actively investigated in clinical trials, each having the potential for combination with the ipilimumab to enhance its effectiveness. Development of rational combinations of immunomodulatory antibodies with small-molecule pathway inhibitor therapies such as vemurafenib makes the discovery of predictive biomarkers even more important. Identifying reliable biomarkers is a necessary step in personalizing the treatment of each patient's cancer through a baseline assessment of tumor gene expression and/or immune profile to optimize therapy for the best chance of therapeutic success.

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Section: Ipilimumab and Possible Predictive Markersmentioning

confidence: 90%

Biomarkers for Immunostimulatory Monoclonal Antibodies in Combination Strategies for Melanoma and Other Tumor Types

Ascierto

Kalos

Schaer

et al. 2013

Clinical Cancer Research

130

View full text Add to dashboard Cite

show abstract

“…Treg cells express CTLA-4 continuously, terminating T cell activation by inhibiting CD28-CD80/86 engagement. The serum level of IL-17 (a potent inflammatory cytokine produced by Th17 cells) is increased in patients with ipilimumabinduced colitis (38) compared to patients without immune-related AEs. An altered Treg cell/Th17 cell axis is critical in the development of many autoimmune diseases, including IBD, psoriatic arthritis (PsA), and many others (36).…”

Section: Treatment Of Immune-related Aes With Checkpoint Inhibitorsmentioning

confidence: 99%

Review: Immune‐Related Adverse Events With Use of Checkpoint Inhibitors for Immunotherapy of Cancer

Suarez‐Almazor

Kim

Abdel-Wahab

et al. 2017

Arthritis & Rheumatology

108

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“…Studies have suggested symptomatic brain metastasis and high body mass index (BMI) as clinical risk factors for the development of irAEs. Moreover, several biomarkers have been linked with irAEs, including high levels of interleukin (IL) 17 in patients with melanoma receiving ipilimumab , eosinophilia , and certain immunologically relevant genes , but additional studies are necessary before any of these biomarkers can be used in the clinic.…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

et al. 2019

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Background Immune‐related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti‐programmed cell death protein 1 (PD‐1) therapy. Materials and Methods All patients with metastatic melanoma and non‐small cell lung cancer (NSCLC) treated with anti‐PD‐1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan‐Meier method and log‐rank test was used for time‐to‐event analysis. Results In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression‐free‐survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. Conclusion Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. Implications for Practice The results of this study suggest that women may be at a higher risk for immune‐related adverse events (irAEs) compared with men when treated with anti‐programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow‐up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment‐related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.

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Evaluation of serum IL-17 levels during ipilimumab therapy: Correlation with colitis.

Cited by 109 publications

References 0 publications

Biomarkers for Immunostimulatory Monoclonal Antibodies in Combination Strategies for Melanoma and Other Tumor Types

Biomarkers for Immunostimulatory Monoclonal Antibodies in Combination Strategies for Melanoma and Other Tumor Types

Review: Immune‐Related Adverse Events With Use of Checkpoint Inhibitors for Immunotherapy of Cancer

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

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