Journal Article

Predictive value of PD-L1 based on mRNA level in the treatment of stage IV melanoma with ipilimumab

Krähenbühl, L., Kirchberger, M. C., Hafner, C., Brüggemann, C., Erdmann, M., Stürzl, M., Dummer, R., Heinzerling, L., Schadendorf, D., Kähler, K. C., Schuler, G., Weide, B., Croner, R. S., Goldinger, S. M., Kiesewetter, F., Leisgang, W., Konrad, A.

2017

Overview

Introduction PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult. In this study, we investigated the PD-L1 gene expression with a new fully automated technique via RT-PCR and correlated the findings with the response to the anti-CTLA-4 antibody ipilimumab. Materials and methods Within a retrospective multi-center trial, PD-L1 gene expression was evaluated in 78 melanoma patients in a total of 111 pre-treatment tumor samples from 6 skin cancer centers and analyzed with regard to response to ipilimumab. For meaningful statistical analysis, the cohort was enriched for responders with 30 responders and 48 non-responders. Gene expression was assessed by quantitative RT-PCR after extracting mRNA from formalin-fixed paraffin embedded tumor tissue and correlated with results from immunohistochemical (IHC) stainings. Results and discussion The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab. The evaluation of PD-L1 expression based on mRNA level is feasible. Correlation between PD-L1 expression as assessed by IHC and RT-PCR showed varying levels of concordance depending on the antibody employed. RT-PCR should be further investigated to measure PD-L1 expression, since it is a semi-quantitative method with observer-independent evaluation. With this approach, there was no statistical significant difference in the PD-L1 expression between responders and non-responders to the therapy with ipilimumab.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Adult / Aged / Aged, 80 and over / Antibodies / B7-H1 Antigen - biosynthesis / B7-H1 Antigen - genetics / B7-H1 Antigen - immunology / Cancer Research / Case-Control Studies / Chemotherapy / CTLA-4 protein / Dacarbazine / Female / Gene Expression / Hematology / Humans / Immunohistochemistry / Immunotherapy / Internal Medicine / Ipilimumab - administration & dosage / L1 gene / Lung cancer / Male / Medical prognosis / Medicine / Medicine & Public Health / Melanoma / Melanoma - drug therapy / Melanoma - genetics / Melanoma - immunology / Melanoma - pathology / MicroRNAs / Middle Aged / Monoclonal antibodies / Neoplasm Staging / Non-small cell lung carcinoma / Oncology / Original Article – Cancer Research / Original – Cancer Research / Paraffin / PD-1 protein / PD-L1 protein / Polymerase chain reaction / Predictive Value of Tests / Real-Time Polymerase Chain Reaction / Retrospective Studies / RNA, Messenger - genetics / RNA, Messenger - metabolism / Skin cancer / Skin Neoplasms - drug therapy / Skin Neoplasms - genetics / Skin Neoplasms - immunology / Skin Neoplasms - pathology / Standardization / Statistical analysis / Targeted cancer therapy