Barbui Tiziano, Carobbio Alessandra, Guglielmelli Paola, Ghirardi Arianna, Fenili Francesca, Loscocco Giuseppe Gaetano, De Stefano Valerio, Ramundo Francesco, Finazzi Maria Chiara, Rambaldi Alessandro, Vannucchi Alessandro M
FROM, Fondazione per la Ricerca Ospedale di Bergamo ETS, Bergamo, Italy.
Dipartimento di Scienze Mediche e Chirurgiche, Materno-Infantili e dell'Adulto, Università di Modena-Reggio Emilia, Modena, Italy.
Br J Haematol. 2024 Dec;205(6):2287-2294. doi: 10.1111/bjh.19813. Epub 2024 Oct 7.
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.
我们在126例被随机分配至真性红细胞增多症（PV）低危期II期试验的患者中，研究了聚乙二醇干扰素α-2b（Ropeg）与单纯放血疗法（Phl-O）对中性粒细胞与淋巴细胞比值（NLR）的影响。基线NLR≥3.5与<3.5的患者相比，PV病史更长，更易出现脾肿大，JAK2V617F变异等位基因频率（VAF）更高（分别为56%和20%，p = 0.001），且疾病增殖性更强。Ropeg在降低NLR方面优于Phl-O（p = 0.008），这种降低主要受中性粒细胞减少的影响，而受淋巴细胞变化的影响较小（分别为-59%和-14%）。这一效应与低危PV主要终点的达成相关（p = 0.021）、症状减轻以及JAK2 VAF降低。有趣的是，JAK2 VAF从基线的降低与NLR的降低呈线性相关。在12个月时对Phl-O治疗无效的患者具有与缓解者不同的特征，包括非常高的NLR以及对每2周交叉使用100μg Ropeg的耐药性，提示需要更高剂量的Ropeg。总之，该研究提供了证据，表明NLR可作为评估和指导低风险PV患者早期使用Ropeg治疗的有价值生物标志物。
