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Gisslinger, H.1, 2; Klade, C.3; Georgiev, P.4; Krochmalczyk, D.5; Gercheva-Kyuchukova, L.6; Egyed, M.7; Rossiev, V.8; Dulicek, P.9; illes, A.10; Pylypenko, H.11; Sivcheva, L.12; Mayer, J.13; Yablokova, V.14; Krejcy, K.15; Grohmann-Izay, B.15; Maurer, G.15; Hasselbalch, H. C.16; Kralovics, R.17; Kiladjian, J.-J.18

doi: 10.1097/01.HS9.0000564092.98639.85
Poster Session II: Myeloproliferative neoplasms - Clinical

1Hematology and Hemostaseology, Medical University of Vienna

2Department of Hematology, Medical University Vienna

3Chief scientific officer, AOP Orphan Pharmaceuticals, Vienna, Austria

4Clinic of Hematology, University Multiprofile Hospital, Plocdiv, Bulgaria

5Teaching Unit of the Hematology Department, University Hospital Krakow, Krakow, Poland

6Clinical Hematology Clinic, Multoprofile Hospital for Active Treatment, Varna, Bulgaria

7Department of Internal Medicine II, Kaposi More Country Teaching Hospital, Kaposvar, Hungary

8Department of Internal Medicine, Samara Kalinin Regional Clinical Hospital, Samara, Russian Federation

9Department of Clinical Hematology, University Hospital Kralove, Hradec Kralove, Czech Republic

10Medical and Health Science Center, University of Deprecen, Deprecen, Hungary

11Regional Treatment and Diagnostics Hematology Center, Cherkasy Regional Onkology Center, Cherkasy, Ukraine

12First Dept. for Internal Medicine, Multiprofile Hospital for Active Treatment, Vratsa, Bulgaria

13Clinic of Internal Medicine - Hematology and Oncology, Universit Hospital Brno, Brno, Czech Republic

14Dept. of Hematology, Yaroslavyl Regional Clinical Hospital, Yaroslavl, Russian Federation

15AOP Orphan Pharmaceuticals, Vienna, Austria

16Department of Hematology, University of Copenhagen, Copenhagen, Denmark

17Dept. of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

18Centre d Investigations Cliniques, Hospital St. Louis and Universite Paris Diderot, Paris, France

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Ropeginterferon alfa-2b (Besremi®; ropegIFN) is a novel mono-pegylated IFNα with an improved application schedule of only every 2-4 weeks. It is the first IFNα with an EU marketing authorization in any of the MPNs and is indicated as first-line monotherapy in high-risk PV patients without symptomatic splenomegaly.

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Here, we present the first randomized long-term head-to-head comparison between ropegIFN and Hydroxyurea (HU) regarding maintenance of response. As the time in hematologic response may be relevant for the risk for thrombosis, it was the aim of the present analysis to compare durations of hematologic response of ropegIFN with HU treated patients in this randomized study.

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254 PV patients (WHO2008 criteria) received ropegIFNor HU in the PROUD-PV Study for 12 months. Thereafter, 89.6% (ropegIFN)and 68.5% (HU) treated patients continued treatment in the CONTINUATION-PV Study. Complete hematological response (CHR) was assessed according to ELN criteria, and maintenance was defined as no change of response status from first time when response was achieved. The tight schedule of assessment visits in these trials ranging from every two weeks in the first year to every 3 months in the third year, allowed for an estimation of cumulative days in response: “days in response” were defined as percentage per overall days on study. Additional efficacy measures, molecular response/disease modification and safety/tolerability have been presented previously (Gisslinger et al., ASH 2018).

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During 3 years of treatment, CHR was achieved and maintained continuously in 38.9% of patients in the ropegIFN but only 14.5% in the control treatment arm (p < 0.05). In line with this finding, duration of CHR was significantly longer in the ropegIFN treatment arm, and the risk to lose response was significantly higher in the control treatment arm (p < 0.0001). The first quartile of response duration in the ropegIFN alfa-2b and control treatment arm was 15.3 months and 6 months, respectively. During the 3rdyear, when both treatment arms had achieved stable response levels, maintenance rates of CHR were 70.5% and 46.1%, respectively for ropegIFN treated vs. patients in the control arm (RR: 1.55 [95% CI: 1.19 to 2.02]; p < 0.01).

In the ropegIFN arm, days in response increased every year from 27.4% in the 1st, to 59.2% in the 2ndand to 75.1% in the 3rdyear. In contrast, patients in the control arm showed quicker onset of response resulting in 44.2% of the days in response during the 1st year, followed by a stabilization at 51.3% during the 2ndand by a slight decrease to 50.2% of the days in response during the 3rdyear of treatment.

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The long-term results focusing on maintenance of CHR in PV patients, showed a clear benefit of ropegIFN (Besremi®) over control (i.e. HU) in (1) achieving significant higher maintenance rates of CHR over the course of treatment, (2) showing a significant lower risk of losing CHR, and (3) presenting significant higher numbers of days in response during each subsequent treatment year vs. a decrease in the control arm. As CHR can be considered as surrogate for risk of thrombosis, these data suggest that RopegIFN is not only the best candidate for disease modification but may in the long run also be an optimal treatment modality for managing risk of thrombosis.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.