ESMO 2026 | FcγR3A germline polymorphism and anti-PD-1 outcomes in melanoma

Yeah, so that’s studied by the NKI group. And what they did was to first assess the genotype, right? We have these three possibilities. So we have the FF, which is the most common, almost 50% of the patients. So phenylalanine in both. And then we have the FV, and that’s when one of them is replaced by valine. And we have the VV, so valine, right? So that one, that is VV, it’s only in 11% of the patients in the general population, and in both arms of the NADINA trial, so the adjuvant arm, nivolumab monotherapy, and neoadjuvant, ipilimumab, okay, neoadjuvantly, in both arms, they saw, in fact, a shorter event-free survival in the patients, a smaller group, of course, so 11%, that they have the genotype VV. So it’s very interesting. The hypothesis is that that variant, that polymorphism, leads to a high affinity receptor. So NK cells, that are the innate immune cells that have that receptor when they have this variant has more higher affinity and they hypothesize that they bind to the nivolumab that is or anti-PD1 that is in fact blocking the T-cells are important right and they that basically that will deplete those cells but those cells are the important ones for the response. So in this case, we see it has a deleterious effect. What is not clear to me, and again, this is very preliminary. I think beautiful data goes a little bit, again, not against, but it’s a bit controversial compared to what we know about the Fc enhancement. But that’s what we like. We want data to challenge what we know because the clinical data is clear, clear cut there’s no question how to put that in the context of what we know that’s what we have to learn right but beautiful data they also showed that all these like it’s we need the treatment to make all the changes of gene expression and in terms of the NK cell and macrophages scores so basically at baseline we don’t see much difference in terms of immune regulators in expression but after treatment we see a distinct big distinction in terms of those patients that have the VV genotype or the FF genotype so beautiful data but I think we need a bit more functional to understand exactly how we can utilize this it’s not clear to me also if this is predictive of treatment or prognostic because could be just prognostic not just like very important but those are the questions that I believe that the team will answer

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