Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera.
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.
Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria;
Heinz
H
Gisslinger
AOP Orphan Pharmaceuticals AG, Vienna, Austria;
Oleh
O
Zagrijtschuk
Sozialmedizinisches Zentrum Ost - Donauspital, Vienna, Austria; Krankenhaus der Elisabethinen Linz, Linz, Austria;
Veronika
V
Buxhofer-Ausch
Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria;
Josef
J
Thaler
Third Medical Department, Hanusch Hospital, Vienna, Austria;
Ernst
E
Schloegl
Department of Internal Medicine V, Hematology & Oncology, Innsbruck Medical University, Innsbruck, Austria;
Guenther A
GA
Gastl
Department of Internal Medicine V, Hematology & Oncology, Innsbruck Medical University, Innsbruck, Austria; Medical Clinic 3, Oncology, Hematology and Rheumatology, University Hospital of Bonn, Bonn, Germany;
Dominik
D
Wolf
Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria; Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;
Robert
R
Kralovics
Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria;
Bettina
B
Gisslinger
Sozialmedizinisches Zentrum Ost - Donauspital, Vienna, Austria;
Karin
K
Strecker
Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria; and.
Alexander
A
Egle
Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria; and.
Thomas
T
Melchardt
Department of Internal Medicine IV, Wels-Grieskirchen Hospital, Wels, Austria;
Sonja
S
Burgstaller
Department of Internal Medicine V, Hematology & Oncology, Innsbruck Medical University, Innsbruck, Austria;
Ella
E
Willenbacher
Department of Internal Medicine I, Division of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria;
Martin
M
Schalling
Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria;
Nicole C
NC
Them
Advanced Drug and Device Services SAS, Brno, Czech Republic.
Pavla
P
Kadlecova
AOP Orphan Pharmaceuticals AG, Vienna, Austria;
Christoph
C
Klade
Laboratory for Immunological and Molecular Cancer Research, Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Paracelsus Medical University, Salzburg, Austria; and.
Richard
R
Greil
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012074:Remission Induction; D015996:Survival Rate
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols