Polycythemia Vera Patients Respond Better to Ropeginterferon Alfa-2b Than HU/BAT Irrespective of Pretreatment or Mutational Status; Results from 5 Years' Treatment in a Randomized, Controlled Setting in the PROUD-PV/Continuation-PV Trials
Authors: Gisslinger Heinz , Klade Christoph , Georgiev Pencho , Krochmalczyk Dorota , Gercheva-Kyuchukova Liana , Egyed Miklos , Dulicek Petr , Illes Arpad , Pylypenko Halyna , Sivcheva Lylia , Mayer Jiri , Yablokova Vera , Krejcy Kurt , Empson Victoria , Hasselbalch Hans C. , Kralovics Robert , Kiladjian Jean-Jacques 
Published: November 2021

Abstract

Introduction:
Ropeginterferon alfa-2b (BESREMi®), a novel pegylated interferon with an extended half-life, was approved in Europe for treatment of patients with PV based on results from the phase 3 PROUD-PV and CONTINUATION-PV trials. Ropeginterferon alfa-2b treatment is recommended in hydroxyurea (HU) naïve patients as well as in those who have previously received HU. Therefore, treatment response was analyzed by prior HU treatment status, and the influence of baseline JAK2V617F allele burden and additional mutations - which may increase over time during non-disease modifying treatment - was explored.
Methods:
In PROUD-PV, patients aged ≥18 years, diagnosed with PV according to WHO 2008 criteria, and either cytoreduction-naïve or HU-pre-treated (for &lt;3 years, without intolerance or resistance) were randomized 1:1 to receive ropeg or HU at individualized doses. After 12 months' treatment, patients could roll over into CONTINUATION-PV and patients in the HU arm were permitted to switch to best available treatment (BAT). After 5 years' treatment, complete hematologic response (CHR) and molecular response defined by modified ELN criteria were assessed in patients enrolled in the extension study CONTINUATION-PV (N=171). Sub-group analyses were performed by prior HU treatment, JAK2V617F allele burden category (≤50% or&gt;50%), and in patients with available data (N=159), by the presence of non-driver mutations (TruSight™ Myeloid Panel, Illumina) or chromosomal aberrations (Affymetrix SNP6.0 array) at baseline.
Results:
After 5 years of treatment with ropeginterferon alfa-2b, high rates of CHR were sustained in both HU-naïve and HU pre-treated patients (53.1% and 61.3%, respectively), whereas in the control arm, the CHR rate was lower among HU pre-treated patients (36.0% compared to 48.0% for HU-naïve patients). Molecular response rates at 5 years in HU naïve and pre-treated patients were 71.4% and 64.5% respectively in the ropeginterferon alfa-2b arm and 26.0% versus 12.5% respectively in the control arm. Rates of adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to discontinuation were similar between the subgroups regardless of HU pre-treatment.
Similar CHR rates were observed at 5 years irrespective of baseline JAK2V617F allele burden category (ropeginterferon alfa-2b arm: 57.1% versus 53.1% for allele burden ≤50% or &gt;50%, respectively; control: 46.9% versus 38.5%, respectively). The molecular response rate in the ropeginterferon alfa-2b arm was higher among patients with baseline allele burden &gt;50% (84.4% versus 61.3% for allele burden ≤50%); in the control arm there was no difference in molecular response rates between the allele burden subgroups (23.1% versus 20.8%, respectively). Of interest, the presence of non-driver mutations or chromosomal aberrations at baseline had no apparent influence on molecular response rates to ropeginterferon alfa-2b (64.5% compared with 70.7% in patients without these genetic abnormalities).
Conclusion:
High hematologic and molecular response rates in both HU-pretreated and HU-naïve patients and in those with more advanced JAK2V617F burden suggest that ropeginterferon alfa-2b is also a suitable treatment option in patients switching from HU.

Disclosures
Gisslinger: AOP Orphan Pharmaceuticals GmbH: Other: Personal fees, Research Funding; Novartis: Other: Personal fees, Research Funding; PharmaEssentia: Other: Personal fees; MyeloPro Diagnostics and Research: Other: Personal fees; Janssen-Cilag: Other: Personal fees; Roche: Other: Personal fees; Celgene: Other: Personal fees. Klade: AOP Orphan Pharmaceuticals GmbH: Current Employment. Pylypenko: Communal nonprofit enterprise "Cherkasy regional oncology dispensary of Cherkasy oblast council: Current Employment. Mayer: AOP Orphan Pharmaceuticals GmbH: Research Funding. Krejcy: AOP Orphan Pharmaceuticals GmbH: Current Employment. Empson: AOP Orphan Pharmaceuticals GmbH: Current Employment. Hasselbalch: Novartis, AOP Orphan: Consultancy, Other: Advisory Board. 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 holder of individual stocks in a privately-held company. Kiladjian: Novartis: Membership on an entity's Board of Directors or advisory committees; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Other: Personal fees; Taiho Oncology, Inc.: Research Funding.