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 .

• Authors: Mirjam Fässler, Stefan Diem, Joanna Mangana, Omar Hasan Ali, Fiamma Berner, David Bomze, Sandra Ring, Rebekka Niederer, Cristina Del Carmen Gil Cruz, Christian Ivan Pérez Shibayama, Michal Krolik, Marco Siano, Markus Joerger, Mike Recher, Lorenz Risch, Sabine Güsewell, Martin Risch, Daniel E Speiser, Burkhard Ludewig, Mitchell P Levesque, Reinhard Dummer, Lukas Flatz
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 7 Issue 1 Pg. 50 (02 20 2019) ISSN: 2051-1426 [Electronic] England
• PMID: 30786924 (Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antibodies, Neoplasm
• Antineoplastic Agents, Immunological
• Biomarkers
• Immunoglobulin G
• Ipilimumab
• Nivolumab
• pembrolizumab

Topics

• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Antibodies, Neoplasm (blood)
• Antineoplastic Agents, Immunological (therapeutic use)
• Biomarkers
• Female
• Humans
• Immunoglobulin G (blood)
• Ipilimumab (therapeutic use)
• Male
• Melanoma (blood, drug therapy, immunology)
• Middle Aged
• Nivolumab (therapeutic use)