EHA 2025 | The impact of clinical signs & symptoms on outcomes in PV treated with hydroxyurea or ruxolitinib

So at EHA, this year we have presented a poster presentation about the prognostic relevance of European Leukemia Net clinical signs and symptoms in the patients with polycythemia vera treated with frontline hydroxyurea or with second-line ruxolitinib. ELN-defined clinical signs and symptoms include many variables, mainly progressive splenomegaly, persistent or progressive hyperleukocytosis, thrombocytosis, uncontrolled hematocrit, relevant cardiovascular risk factors and also severe itching. 

We have demonstrated and published in Leukemia this year that these features are significantly associated with an increased risk of thrombosis in the patients who receive hydroxyurea in the front line. However, we actually didn’t know whether or not the clinical signs and symptoms defined by the European Leukemia Net could really predict the long-term outcomes in patients with polycythemia vera, particularly transformation to secondary myelofibrosis or acute leukemia. 

So in this real-world study, we analyzed 739 PV patients treated with frontline hydroxyurea and those 254 patients treated with second-line ruxolitinib. Around 60% of these patients actually carried at least one ELN clinical sign and symptom. So this is a kind of frequent situation in our clinical practice. And what we observed is that in the hydroxyurea cohort, the rates of disease progression were not influenced significantly by the presence of the European Leukemia Net clinical signs and symptoms. However, when we analyze separately the patients receiving ruxolitinib, we observe that the presence of clinical signs and symptoms was associated with a significantly increased risk of thrombosis, with a five-year thrombosis-free survival of 95 percent for the patients with clinical signs and symptoms, and 100 percent for the patients without clinical signs and symptoms. So if I treat a patient with ruxolitinib and I have no clinical signs and symptoms, I have a five-year thrombosis-free survival of 100%, zero thrombotic events. 

Similarly, we also observe that the progression-free survival, including progression to secondary myelofibrosis and acute leukemia, was negatively and significantly influenced by the presence of clinical signs and symptoms in the ruxolitinib group. And the gap was very pronounced and significant. 74.9% progression-free survival in patients without clinical signs and symptoms compared to only 9% in the patients with clinical signs and symptoms. 

So if I have to summarize all this, clinical signs and symptoms are strongly associated with an increased thrombotic risk, both when we use hydroxyurea in the frontline and when we use ruxolitinib in the second line. But the main key message of this abstract presentation is that these clinical signs and symptoms are significant predictors of progression into secondary myelofibrosis and acute leukemia in the patients with a more advanced disease who require a second line treatment with ruxolitinib. So my recommendation is to evaluate in your clinical practice, clinical signs and symptoms, because they may provide very powerful and clinically useful information in order to optimize the management of polycythemia vera.

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