In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) α-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 µg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-α. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient.

3rd Medical Department Hanusch Hospital Vienna Austria;

Advanced Drug and Device Services SAS Brno Czech Republic

AOP Orphan Pharmaceuticals AG Vienna Austria;

Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria;

Department of Internal Medicine 1 Division of Hematology and Blood Coagulation Medical University of Vienna Vienna Austria;

Department of Internal Medicine 1 Division of Hematology and Blood Coagulation Medical University of Vienna Vienna Austria; Center for Molecular Medicine of the Austrian Academy of Sciences Vienna Austria;

Department of Internal Medicine 4 Wels Grieskirchen Hospital Wels Austria;

Department of Internal Medicine 5 Hematology and Oncology Innsbruck Medical University Innsbruck Austria;

Department of Internal Medicine 5 Hematology and Oncology Innsbruck Medical University Innsbruck Austria; Medical Clinic 3 Oncology Hematology and Rheumatology University Hospital of Bonn Bonn Germany;

Laboratory for Immunological and Molecular Cancer Research Department of Internal Medicine 3 with Hematology Medical Oncology Hemostaseology Infectious Diseases Rheumatology Oncologic Center Paracelsus Medical University Salzburg Austria; and

Sozialmedizinisches Zentrum Ost Donauspital Vienna Austria;

Sozialmedizinisches Zentrum Ost Donauspital Vienna Austria; Krankenhaus der Elisabethinen Linz Linz Austria;

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ROP-ET: a prospective phase III trial investigating the efficacy and safety of ropeginterferon alfa-2b in essential thrombocythemia patients with limited treatment options

Long-term outcomes of polycythemia vera patients treated with ropeginterferon Alfa-2b

Ropeginterferon Alfa-2b: Efficacy and Safety in Different Age Groups

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ClinicalTrials.gov
NCT01193699