Integrated genomic correlates of response to PD-1 inhibitor nivolumab in mRCC

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Published: 8 Jan 2016
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Dr Guillermo de Velasco - Dana-Farber Cancer Institute, Boston, USA

Dr de Velasco talks to ecancertv at ASCO GU 2016 about his research in to genomic indicators of response to nivolumab for metastatic renal cell carcinoma. 

Nivolumab is a programmed death-1 (PD-1) inhibitor that has recently been shown to increase overall survival in patients with mRCC.

The association between benefit from nivolumab with neoantigen load, mutation load and signatures of immune infiltration is an interesting area for investigation.

This analysis suggests that both DNA- and RNA-level data may be relevant for explaining clinical benefit from nivolumab in mRCC.

In contrast with results from other tumour types, responders to nivolumab did not have more mutated tumours, though immune-related gene expression may be related to response.

Basically we know now that there is a new drug approved for metastatic renal cell carcinoma, nivolumab, this anti-PD-1 but the issue is that most of the time we don’t have a real biomarker to predict response. So what we did, we selected nine patients treated with anti-PD-1 and we collected the tissue before treatment. What we do is we try to find neoantigens or mutational loads as predictors of response for this treatment. The main concern is that we have only nine patients so it’s a very small sample to get a real conclusion but initially what we have seen is that probably new antigens may have a role though not the mutational load.

What did you find?

Yes, so what we found is that patients with the neoantigens, the level of neoantigens might predict the response to nivolumab. However, there is only a few patients so we cannot get a very robust conclusion about that. What we also did in this small sample is we were looking at specific cytolytic activity and what we saw is that in specific patients with a complete response that were in treatment for more than 13 months in response, he had a high cytolytic activity compared to the rest of the patients.

What are the potential implications?

I think now what we are doing currently is we are trying to do a multi-institutional study trying to gather more samples from different institutions. The main objective of that study is to try to get a real conclusion that might be applied to the rest of the patients, like to get a real conclusion to be applied to our patients treated with nivolumab.