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4563 Individualized Dosing of Ropeginterferon Alfa-2b Ensures Optimal Response in Patients with Low-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, drug development, Diseases, Therapies, Immunotherapy, Adverse Events, Myeloid Malignancies, Study Population, Human
Monday, December 11, 2023, 6:00 PM-8:00 PM

Heinz Gisslinger, MD1*, Christoph Klade, PhD2*, Pencho Georgiev3*, Dorota Krochmalczyk, MD4*, Liana Gercheva-Kyuchukova, MD5*, Miklos Egyed, MD6*, Petr Dulicek, MD7*, Arpad Illes, MD8*, Halyna Pylypenko, MD9*, Liliya Sivcheva, MD10*, Jiri Mayer, Prof, MD11, Vera Yablokova, MD12*, Kurt Krejcy, MD2*, Victoria Empson, MSc13*, Hans Hasselbalch, MD14*, Robert Kralovics, PhD15* and Jean-Jacques Kiladjian, MD, PhD16

1Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria
2AOP Health, Vienna, Austria
3Medical University of Plovdiv, Plovdiv, Bulgaria
4Department of Hematology, Collegium Medicum, Jagiellonian University, Krakow, Poland
5Multiprofile Hospital For Active Treatment "Sveta Marina", Varna, Bulgaria
6Somogy County Mór Kaposi General Hospital, Kaposvár, Hungary
7Department of Clinical Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic
8Department of Hematology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
9Department of Hematology, Regional Treatment and Diagnostics Hematology Centre, Cherkasy Regional Oncology Centre, Cherkasy, Ukraine
10First Department of Internal Medicine, Multiprofile Hospital for Active Treatment - HristoBotev, Vratsa, Bulgaria
11Clinic of Internal Medicine - Hematology and Oncology, University Hospital Brno, Brno, Czech Republic
12Department of Hematology, Yaroslavl Regional Clinical Hospital, Yaroslavl, Russian Federation
13AOP Health, Vienna, Vienna, Austria
14Roskilde Hospital, University of Copenhagen, Copenhagen, Denmark
15Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
16Université de Paris, AP-HP, Hôpital Saint-Louis, Centre d’Investigations Cliniques, Paris, France


Ropeginterferon alfa-2b at a fixed dose of 100 µg/2 weeks was efficacious in patients with low-risk polycythemia vera (PV) in the Low-PV trial, but the response rate was lower in a group of patients who switched to ropeginterferon alfa-2b after failing to respond to phlebotomy alone (Barbui et al., 2023). The finding that this group had a higher proportion of males and higher baseline values for body-mass index, phlebotomy demand, blood counts and JAK2V617F allele burden suggests that these characteristics might predict a higher dose requirement of ropeginterferon alfa-2b. We analyzed low-risk PV patients from the PROUD-PV/CONTINUATION-PV (NCT01949805/NCT02218047) cohort to examine the impact of baseline characteristics and individually optimized dose levels of ropeginterferon alfa-2b on response status at 12, 24 and 72 months.


Patients diagnosed with PV (WHO 2008 criteria) were randomized 1:1 and received ropeginterferon alfa-2b or standard care for a total of ≥6 years during the 12-month PROUD-PV study and its extension CONTINUATION-PV. Low-risk patients (aged ≤60 years with no history of thrombosis) allocated to the ropeginterferon alfa-2b arm were analyzed. Ropeginterferon alfa-2b was started at a dose of 100 µg/2 weeks (50 µg if transitioning from hydroxyurea) and escalated by 50 µg/2 weeks until blood counts normalized to a maximum of 500 µg/2 weeks. Grade 2-3 drug-related toxicity mandated dose reduction/interruption. During maintenance treatment the dosing interval could be extended to 3-4 weeks. Complete hematologic response (CHR) defined by modified ELN criteria (without the spleen criterion) and safety data at 12, 24 and 72 months were assessed.


In the setting of individualized dosing, 33/56 (58.9%) low-risk PV patients allocated to ropeginterferon alfa-2b in PROUD-PV achieved a CHR at month 12. Response rates increased with longer treatment duration; of the 46 low-risk patients enrolled in CONTINUATION-PV; 80.4% and 73.2% of patients with available data achieved a CHR at months 24 and 72, respectively.

Baseline characteristics by response status at month 12 indicated that males were overrepresented among non-responders (15/23 non-responders [65.2%] were male vs 11/33 responders [33.3%] [p=0.0291]), and baseline median JAK2V617F allele burden was non-significantly higher in non-responders at 12 months (45.6% vs 35.5%: p=0.1860). However, no significant differences in these baseline parameters were observed by long-term response status (24 months or 72 months), nor were there consistent differences in baseline body mass index or blood counts according to response status at any time point evaluated.

The most frequent reason for non-response was failure to meet the CHR criterion hematocrit <45% without phlebotomy in the past 3 months, accounting for the majority of non-responders at months 12, 24 and 72 (13/23 [56.5%], 6/9 [66.7%], and 6/11 [54.5%], respectively), followed by discontinuation for any reason, which accounted for 30.4% of non-responders at month 12 and 36.4% at month 72. Only one low-risk patient discontinued due to ropeginterferon alfa-2b-related toxicity.

Despite response-driven dosing, the median 4-weekly derived dose of ropeginterferon alfa-2b in the first year was only somewhat higher in non-responders compared with responders (809 µg [range: 209-898] vs 717 µg [188-898]; p=0.6954); 10/23 of non-responders at month 12 did not escalate the dose immediately according to protocol on ≥1 occasion during the first year, e.g. due to responses already observed for leukocyte or platelet counts. In the second year, the median 4-weekly doses were 997 µg (range: 211-997) vs 690 µg (88-1036) respectively (p=0.2024), indicating that non-responders received and tolerated the maximum dose (500 µg/2 weeks).


High long-term response rates (80.4% at 24 months; 73.2% at 72 months) were achieved with ropeginterferon alfa-2b treatment in the low-risk PV population when the dose was optimized on an individual basis. No specific baseline characteristics among low-risk PV patients appear to be associated with long-term response to ropeginterferon alfa-2b. However, the PROUD-PV/CONTINUATION-PV studies show that - as hypothesized based on the Low-PV trial data - some low-risk patients require and can tolerate high doses, and that the optimal dose of ropeginterferon alfa-2b varies substantially between patients.

Disclosures: Gisslinger: AOP Health: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; PharmaEssentia: Honoraria; BMS: Honoraria. Klade: AOP Health: Current Employment. Georgiev: UMHAT St George: Current Employment; Medical University Plovdiv: Current Employment; Bristol Myers Squibb: Other: Speaker; Novartis: Other: Speaker; Roche: Other: Speaker. Illes: Pfizer: Consultancy, Other: travel and conference support; Novartis: Consultancy, Other: travel and conference support; Takeda: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Other: travel and conference support; AbbVie: Consultancy; Roche: Consultancy, Other: travel and conference support. Krejcy: AOP Health: Current Employment. Empson: AOP Health: Current Employment. Hasselbalch: AOP Health: Honoraria; Novartis: Honoraria. Kralovics: AOP Health: Honoraria; PharmaEssentia: Honoraria; Qiagen: Honoraria; Novartis: Honoraria; MyeloPro Diagnostics and Research: Current equity holder in private company. Kiladjian: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; AbbVie, AOP Health, Bristol-Myers Squibb, GlaxoSmithKline, Incyte, Novartis, Pharmaessentia.: Consultancy.

*signifies non-member of ASH