Neutrophil/lymphocyte ratio identifies low-risk polycythaemia vera patients for early Ropeginterferon alfa-2b therapy

We investigated the effect of Ropeginterferon alfa-2b (Ropeg) versus phlebotomy-only (Phl-O) on the neutrophil-to-lymphocyte ratio (NLR) in 126 patients randomized in the low-polycythaemia vera (PV) phase II trial. Patients with a baseline NLR ≥3.5 vs. <3.5 had a longer history of PV, were more likely to have splenomegaly, higher JAK2V617F variant allele frequency (VAF) (56% vs. 20% p = 0.001) and more proliferative disease. Ropeg was superior to Phl-O in reducing NLR (p = 0.008), and the reduction was strongly influenced by the reduction in neutrophils and less by a change in lymphocytes (-59% and -14% respectively). This effect was associated with the achievement of the low-PV primary end-point (p = 0.021), symptom reduction and reduction in JAK2 VAF. Interestingly, the reduction in JAK2 VAF from baseline was linearly associated with the reduction in NLR. Patients who failed Phl-O at 12 months had characteristics that distinguished them from responders, including very high NLR and resistance to cross-over to 100 μg Ropeg every 2 weeks suggesting higher escalated doses of Ropeg. In conclusion, the study provides evidence that NLR can serve as a valuable biomarker to assess and guide treatment with Ropeg in the early stage of low-risk PV patients.