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Ruxolitinib and interferon-a for PV and MF
could greatly improve the quality of life of patients with myeloproliferative neoplasms. Moreover, the risk of thrombosis is greatest shortly after diagnosis, and aggres- sive initial treatment may reduce the risk of early throm- bosis.49 To this end, a new phase II study investigating combination therapy in newly diagnosed PV patients has been initiated (#EudraCT2018-0041-50).
One strength of our study is the investigation of bone marrow remissions, which is essential in assessing a pos- sible disease-modifying effect of new treatments.34,35 Additionally, we used the validated MPN-SAF question- naire to assess the symptom burden during the treatment. In patients with myeloproliferative neoplasms, in whom it is essential to balance the efficacy of a treatment with its toxicity, quality of life is a clinically relevant end- point.34,35 Furthermore, we used a highly sensitive method to assess the JAK2 V617F allele burden.32 A limitation of our study is the relatively small population of MF patients. Accordingly, results in this group should be interpreted with caution. Moreover, the study lacked a dose-finding phase I part, which would have been rele- vant. Furthermore, the study was planned for 2 years of treatment, but hematologic and histological responses have been observed after several years of PEG-IFNa treat-
ment, and the response after 2 years may underestimate the long-term clinical effect.28,29,37,38 Most patients on com- bination treatment at the end of the study continued treatment and post-hoc analyses with longer follow-up are being planned to assess the long-term response to combination treatment.
In conclusion, combination treatment with ruxolitinib and low-dose PEG-IFNa2 improved peripheral blood cell counts, bone marrow cellularity and fibrosis along with symptom burden with acceptable toxicity in some patients with PV and proliferative MF. Most patients in the study were intolerant of or refractory to standard PEG- IFNa2 treatment, and more than half had discontinued previous treatment with hydroxyurea, highlighting that this combination treatment is a viable choice for patients with few treatment options left.
Acknowledgments
The authors thank the patients and their families and the research staff. Danish Telemedicine A/S developed the software system for the online MPN-SAF questionnaire. We thank Associate Professor Julie Lyng Formann from the Section of Biostatistics, University of Copenhagen, for guidance in repeated measurements statistics.
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