Dataset Information

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients.

ABSTRACT:

Background

Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed.

Methods

We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts. In cohort 1, a prospective study, we measured specific antibodies before treatment, after one week and after six to nine weeks of treatment. Cohort 2 consisted of serum samples prior to CI therapy initiation. ELISA assays were performed to quantify specific IgG directed against melanocyte differentiation antigens tyrosinase-related proteins 1 and 2 (TRP1/TYRP1 and TRP2/TYRP2), glycoprotein 100 (gp100), MelanA/MART1, and the cancer-testis antigen NY-ESO-1. Response was defined as either complete or partial remission on CT scan according to RECIST 1.1.

Results

In cohort 1, baseline levels of these antibodies were higher in the responder group, although statistical significance was only reached for NY-ESO-1 (p =?0.007). In cohort 2, significantly higher antibody baseline levels for MelanA/MART1 (p =?0.003) and gp100 (p =?0.029) were found. After pooling the results from both cohorts, higher levels of MelanA/MART1 (p =?0.013), TRP1/TYRP1 (p =?0.048), TRP2/TYRP2 (p =?0.047) and NY-ESO-1 (p =?0.005) specific antibodies at baseline were independently associated with response.

Conclusions

Melanoma-associated antibodies may be candidate biomarkers for response and survival in metastatic melanoma patients being treated with CIs. These markers may be used to complement patient assessment, in combination with PD-L1 status, tumor-infiltrating lymphocytes and tumor mutational burden, with the aim to predict outcome of CI treatment in patients with metastatic melanoma.

Trial registration

Ethikkommission Ostschweiz, EKOS 16/079 https://ongoingprojects.swissethics.ch/runningProjects_list.php?q=%28BASECID~contains~2016-00998%29&orderby=dBASECID .

SUBMITTER: Fassler M

PROVIDER: S-EPMC6383238 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients.

Fässler Mirjam M Diem Stefan S Mangana Joanna J Hasan Ali Omar O Berner Fiamma F Bomze David D Ring Sandra S Niederer Rebekka R Del Carmen Gil Cruz Cristina C Pérez Shibayama Christian Ivan CI Krolik Michal M Siano Marco M Joerger Markus M Recher Mike M Risch Lorenz L Güsewell Sabine S Risch Martin M Speiser Daniel E DE Ludewig Burkhard B Levesque Mitchell P MP Dummer Reinhard R Flatz Lukas L

Journal for immunotherapy of cancer 20190220 1

<h4>Background</h4>Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed.<h4>Methods</h4>We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts. In cohort 1, a prospective study, we measured specific antibodies before treatment, after one week and after six to nine weeks of tre ...[more]

PMID: 30786924

Similar Datasets

Project description:BACKGROUND:Immune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1 molecules, have shown impressive therapeutic results. However, only 20-40% of advanced melanoma patients have durable responses to ICI, and these positive effects must be balanced against severe off-target immune toxicity and high costs. This urges the development of predictive biomarkers for ICI response to select patients with likely clinical benefit from treatment. Although many candidate biomarkers exist, a systematic overview of biomarkers and their usefulness is lacking. OBJECTIVES:Here, we systematically review the current literature of clinical data of ICI treatment to provide an overview of candidate predictive biomarkers for ICI in melanoma patients. METHODS:To identify studies on biomarkers for clinical response or survival to ICI therapy in melanoma patients, we performed a systematic search in OVID MEDLINE and retrieved 429 publications, of which 67 met the eligibility criteria. RESULTS:Blood and genomic biomarkers were mainly studied for CTLA-4 ICI, while tumor tissue markers were analyzed for both CTLA-4 and PD-1 ICI. Blood cytology and soluble factors correlated more frequently to overall survival (OS) than to response, indicating their prognostic rather than predictive nature. Systemic T-cell response and regulation markers correlated to response, but progression-free survival or OS were not analyzed. Tumor tissue analyses revealed response correlations with mutational load, neoantigen load, immune-related gene expression, and CD8+ T-cell infiltration at the invasive margin. The predictive value of PD-L1 varied, possibly due to the influence of T-cell infiltration on tumor PD-L1 expression. Genomic biomarker studies addressed CTLA-4 and other immune-related genes. CONCLUSION:This review outlines all published biomarkers for ICI therapy and highlights potential candidate markers for future research. To date, PD-L1 is the best studied biomarker for PD-1 ICI response. The most promising candidate predictive biomarkers for ICI response have not yet been identified. Variations in outcome parameters, statistical power, and analyses hampered summary of the results. Further investigation of biomarkers in larger patient cohorts using standardized objectives and outcome measures is recommended.

Dataset Information

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients.

Background

Methods

Results

Conclusions

Trial registration

Publications

Antibodies as biomarker candidates for response and survival to checkpoint inhibitors in melanoma patients.

Similar Datasets

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