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4345 Efficacy and Safety of Long-Term Ropeginterferon Alfa-2b Treatment in Patients with Low-Risk and High-Risk Polycythemia Vera (PV)

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, adult, MPN, Clinical Research, Chronic Myeloid Malignancies, Diseases, Therapies, Adverse Events, Myeloid Malignancies, Study Population, Human
Monday, December 12, 2022, 6:00 PM-8:00 PM

Jean-Jacques Kiladjian, MD1, Christoph Klade, PhD2*, Pencho Georgiev, MD3*, Dorota Krochmalczyk, MD4*, Liana Gercheva-Kyuchukova, MD5*, Miklos Egyed, MD, PhD6*, Petr Dulicek, MD7*, Arpad Illes, MD8*, Halyna Pylypenko, MD9*, Lylia Sivcheva, MD10*, Jiří Mayer, MD11, Vera Yablokova, MD12*, Kurt Krejcy, MD2*, Victoria Empson, MSc13*, Hans Carl Hasselbalch, MD14, Robert Kralovics, PhD15 and Heinz Gisslinger, MD16*

1Centre d'Investigations Cliniques (INSERM CIC 1427), AP-HP, Hôpital Saint-Louis, Université Paris Cité, Paris, France
2AOP Orphan Pharmaceuticals GmbH, Vienna, Austria
3Medical University of Plovdiv, Plovdiv, Bulgaria
4Teaching Unit of the Hematology Department, University Hospital in Krakow, Kracow, Poland
5Clinical Hematology Clinic, Multiprofile Hospital for Active Treatment "Sveta Marina", Varna, Bulgaria
6Department of Internal Medicine II, Kaposi Mor County Teaching Hospital, Kaposvar, Hungary
7Department of Clinical Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
8Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
9Regional Treatment and Diagnostics Haematology Centre, Cherkassy Regional Council, Cherkassy, Ukraine
10First Department of Internal Medicine, Multiprofile Hospital for Active Treatment - HristoBotev, Vratsa, Bulgaria
11Clinic of Internal Medicine-Haematology and Oncology, University Hospital Brno, Brno, Czech Republic
12Department of Hematology, Yaroslavl Regional Clinical Hospital, Yaroslavl, Russian Federation
13AOP Orphan Pharmaceuticals GmbH, Vienna, Vienna, Austria
14Department of Hematology, Zealand University Hospital, Roskilde, Denmark
15Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
16Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University Vienna, Vienna, Austria


Patients with “low-risk” (LR) PV are managed conservatively despite higher risk of vascular events and impaired quality of life compared to a population without PV. Acknowledging new evidence (LOW-PV study, Barbui et al 2021), recent treatment guidelines (European LeukemiaNet [ELN] 2021) recommend ropeginterferon alfa-2b (BESREMi®) as a cytoreductive treatment in LR PV patients meeting specific criteria as well as in high-risk (HR) PV patients. Final data from the phase 3 PROUD-PV and CONTINUATION-PV trials (NCT01949805; NCT02218047) demonstrated the long-term efficacy and safety of ropeginterferon alfa-2b compared with hydroxyurea/best available treatment (HU/BAT); here we report results in the ropeginterferon alfa-2b arm by risk stratum.


PV patients were randomized 1:1 and received ropeginterferon alfa-2b or HU/BAT for ≥6 years. In the ropeginterferon alfa-2b arm, subgroup analyses were performed post-hoc by risk stratum (LR: age ≤60 years and no history of thrombosis; all others HR). Complete hematologic response (CHemR) and molecular response defined by modified ELN criteria were assessed in the full analysis set for CONTINUATION-PV (N=95); safety analyses included all data regardless of roll-over (N=127).


CONTINUATION-PV enrolled 46 LR and 49 HR patients in the ropeginterferon alfa-2b arm. At baseline, mean age was 50.7 vs 63.7 years respectively, and median duration since PV diagnosis was 1.9 months vs 1.5 months. HR patients had higher platelet and leukocyte counts at baseline and more frequently presented with clinically significant splenomegaly or PV-related symptoms. Median JAK2V617F allele burden was similar for LR and HR patients (37.0% vs 39.4%), however LR patients were less likely to harbor additional non-driver mutations (11.4% vs 24.4%).

The median 4-weekly ropeginterferon alfa-2b dose was comparable in LR and HR patients throughout the study (in the 6th year, 499 µg and 489µg respectively) as was the use of an extended 3-4 weekly dose regimen (6th year: 59.5% vs 65.4%).

LR patients achieved a significantly higher CHemR rate than HR patients during long-term treatment (Month 72: 73.2% vs 38.3% in LR and HR respectively [RR: 2.41; 95% CI: 1.50 to 3.90; p=0.0003]). Higher CHemR among LR patients was confirmed in a sensitivity analysis including discontinued patients (last observation carried forward [LOCF]; 80.4% in LR vs 65.3% in HR patients at Month 72) indicating that in the HR group, more patients discontinued despite CHemR. In general, discontinued patients were older than those who completed the study (mean age 62.8 years vs 55.2 years) but did not have a longer duration of PV or markedly greater symptom burden at baseline.

Importantly, regardless of risk stratum, most patients receiving ropeginterferon alfa-2b did not require any phlebotomy for the entire 6th year (85.7% of LR patients and 75.0% of HR patients entering the 6th year [p=0.3]).

LR patients had a higher molecular response rate than HR patients (LOCF at Month 72: 84.4% vs 49.0% respectively, RR: 2.15 [95% CI: 1.37 to 3.37]; p=0.0009) and achieved molecular response more rapidly (median time to first response: 12 months [95% CI: 12 to 18] vs 18 months [95% CI: 12 to 24]; Log-rank test p=0.03). The median JAK2V617F allele burden was 5.6% for LR and 17.9% for HR patients at Month 72 (p<0.0001).

During the entire PROUD-PV/CONTINUATION-PV studies (≥6 years exposure), adverse drug reactions (ADRs) to ropeginterferon alfa-2b led to withdrawal of treatment in 1 (1.8%) LR patient (due to sarcoidosis), and in 13 (18.3%) HR patients (due to thrombocytopenia [n=1], elevated transaminases [n=1], psychiatric disorders [n=2], autoimmune disorders [n=6], hypothyroidism [n=2] and dyspnea/pneumonitis [n=1]). LR patients were also less likely than HR patients to experience ADRS of grade ≥3 severity (5.4% vs 23.9%).


These results demonstrate the benefit of ropeginterferon alfa-2b therapy in both HR and LR patient populations. LR patients may have a greater potential benefit: higher hematologic and molecular response rates can be safely achieved, and the patients are more likely to remain on long-term treatment. These data provide further evidence for an early treatment start as recently outlined by the updated ELN guidelines.

Disclosures: Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Klade: AOP Orphan Pharmaceuticals GmbH: Current Employment. Krejcy: AOP Orphan Pharmaceuticals GmbH: Current Employment. Empson: AOP Orphan Pharmaceuticals GmbH: Current Employment. Hasselbalch: AOP Orphan Pharmaceuticals: Consultancy, Other: Data monitoring board; Novartis: Consultancy, Other: Grants. Kralovics: AOP Orphan Pharmaceuticals GmbH: Other: Personal fees; PharmaEssentia: Other: Personal fees ; Qiagen: Other: Personal fees ; Novartis: Other: Personal fees; MyeloPro Diagnostics and Research: Current equity holder in private company. Gisslinger: BMS: Other: Personal fees; PharmaEssentia: Other: Personal fees ; Novartis: Other: Grants and personal fees ; AOP Orphan Pharmaceuticals GmbH: Other: Grants and personal fees .

*signifies non-member of ASH