Myeloproliferative neoplasms treated with hydroxyurea, pegylated interferon alpha-2A or ruxolitinib: clinicohematologic responses, quality-of-life changes and safety in the real-world setting

<b>Introduction:</b> Real-world data of responses, quality-of-life (QOL) changes and adverse events in patients with myeloproliferative neoplasms (MPN) on conventional therapy (hydroxyurea ± anagrelide), pegylated interferon alpha-2A (PEG-IFNα-2A) or ruxolitinib are limited. <b>Methods:</b> We prospectively studied MPN patients receiving conventional therapy, PEG-IFNα-2A or ruxolitinib. Next-generation sequencing of 69 myeloid-related genes was performed. Clinicohematologic responses, adverse events, and QOL (determined by the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score, MPN-SAF TSS) were evaluated. <b>Results:</b> Seventy men and fifty-five women with polycythemia vera (PV) (<i>N</i> = 23), essential thrombocythemia (ET) (<i>N</i> = 56) and myelofibrosis (MF) (<i>N</i> = 46) were studied for a median of 36 (range: 19–42) months. In PV, responses were comparable for different modalities. <i>CREBBP</i> mutations were associated with inferior responses. In ET, PEG-IFNα-2A resulted in superior clinicohematologic complete responses (CHCR) (<i>P </i>= 0.045). In MF, superior overall response rates (ORR) were associated with ruxolintib (<i>P </i>= 0.018) and <i>JAK2</i>V617F mutation (<i>P </i>= 0.04). For the whole cohort, ruxolitinib led to rapid and sustained reduction in spleen size within the first 6 months, and significant improvement of QOL as reflected by reduction in MPN-SAF TSS (<i>P</i> &lt; 0.001). Adverse events of grades 1–2 were observed in 44%, 62% and 20% of patients receiving conventional therapy, PEG-IFNα-2A and ruxolitinib respectively; and of grade 3–4 in 7% and 9% of patients receiving PEG-IFNα-2A and ruxolitinib. <b>Conclusions:</b> Conventional therapy, PEG-IFNα-2A and ruxolitinib induced responses in all MPN subtypes. PEG-IFNα-2A led to superior CHCR in ET; whereas ruxolitinib resulted in superior ORR in MF, and significant reduction in spleen size and improvement in QOL.