MPN Workshop of the Carolinas 2025 | Neutrophil-to-lymphocyte ratio: a potential dynamic biomarker of treatment response in PV

Yeah, so we just published this with Tiziano Barbui from Italy, and the neutrophil-lymphocyte ratio is exactly that. When you get a complete blood count with a differential blood cell count, you get a number of lymphocytes per microliter, a number of neutrophils per microliter in the blood count, so the concentration of the cells, if you will. And if you just take the ratio of those two things, that’s the neutrophil lymphocyte ratio. So straightforward in terms of how to measure it. The benefit there is that every time you get a CBC, a blood count, you get an NLR, neutrophil-lymphocyte ratio. So it has a convenience factor. It doesn’t add extra cost. 

And the NLR has actually been widely used and validated in other diseases. So in cardiovascular disease, an elevated NLR is associated with an increased risk of cardiovascular events. And in cancer, it’s a general marker of worse prognosis. And so what we looked at, and this is really driven by Tiziano Barbui, but he has run some of these bigger clinical trials, and so we had this clinical trial data. So this is kind of the gold standard in any investigation is trying to get patients who are otherwise identical, except for what you’re testing. And so clinical trials, that’s the way they’re designed. So we had that data and we were able to then look at, well, in those people who had a high NLR versus a low NLR, you know, how do they do? And then the more important part of the studie is, frankly, is we looked at different drugs, different therapies. So in polycythemia vera, some people are treated with just phlebotomy alone. Some people are treated with cytoreductive therapies. Cytoreductive therapies can include drugs like hydroxyurea and interferon. So we looked at all three of those. 

And as it turns out, phlebotomy alone actually increases NLR, which is, at least by that measure, a bad thing. Hydroxyurea actually keeps NLR the same. So it doesn’t make people with a high NLR back to normal. It just kind of moves everything together. So it’ll reduce the lymphocyte count and the neutrophil count kind of together. So NLR, which the ratio stays the same. Whereas interferons kind of do something special and unique among those drugs that we looked at, is they will reduce the neutrophil count, but the lymphocyte counts remain relatively stable. And so that combination can reduce the NLR. And then when we looked at people who had a reduction in NLR, they also had a deep molecular response. So proportion of NLR reduction correlated with molecular, you know, the JAK2 mutation burden reduction and outcomes. When we looked at events, people who had their NLR lower did better than those people who didn’t. So I think it’s kind of a good marker because it doesn’t add any cost. It’s just something to pay attention to. And I think we still have more to learn about it, but it is pointing to be a biomarker that’s both available and of value.

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