ASCO 2015

Screening to identify unsuitable candidates for ipilimumab in advanced melanoma

Dr Pier Francesco Ferrucci - European Institute of Oncology, Milan, Italy

Baseline neutrophils in patients treated with ipilimumab, what’s it all about?

You know that using immunotherapy and ipilimumab in particular it’s a question of identifying the patients who would be more prone to respond to treatment. The story of the search for biomarkers is one of the most important nowadays, especially for what depends on immunotherapy. So what we were trying to do was to identify a method, or let’s say an algorithm, in order to better identify those patients who would be more prone to respond to the treatment.

So can you tell me what you did to establish this?

Yes, firstly we evaluated around 70 patients that we treated in our institution with ipilimumab, patients affected by advanced or metastatic melanoma. We evaluated the number of neutrophils at baseline and then we made the ratio with lymphocytes in order to understand what could be the impact of the microenvironment on the treatment and on the response.

What put you on to the idea of looking at baseline neutrophils?

There are a few works already published in other kinds of tumours and in some cases they were able to identify those patients who were responders versus not responders. So we applied this algorithm, this ratio, and we showed that there was the possibility to identify, really identify, patients who respond better to the treatment. So we went forward and we evaluated 720 patients which were treated within the expanded access programme in Italy and we tried to confirm this data and we succeeded to confirm this data.

Clearly if you know patients who are not going to respond you can spare toxicity and cost, so how good was your test?

We think that the test was really good and very easy, which could be done in every hospital. It just needs a little basic evaluation on the sensibility and the specificity, so statistical necessity to be really applied. But it’s very informative and easy to perform.

So neutrophils high and ratio high is bad for using ipilimumab?

Yes, it seems so. It seems so and we are going forward because we were trying to combine this data, this information also with other known prognostic or predictive factors like LDH, like performance status. We were able to divide the patients into three different cohorts and, to make an example, those who were in the best, let’s say, cohort in order to be responding are alive after one year in 43% of cases and after two years more than 25%. So we think that with this method we are able to identify those patients who followed the curve, the plateau, and it’s possible to identify the long responders.

So what clinical message would you give to doctors at this point?

The message is just to take advantage of this information and to apply before therapy and to offer this treatment mainly to those patients who have specific characteristics. We are going to have a lot of new drugs available and so we are trying to identify the section in which each one of them could be more efficacious.