Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera

作者：Heinz Gisslinger, Oleh Zagrijtschuk, Veronika Buxhofer‐Ausch, Josef Thaler, Ernst Schloegl, Guenther A. Gastl, Dominik Georg Friedrich Wolf, Róbert Královics, Bettina Gisslinger, Karin Strecker, Alexander Egle, Thomas Melchardt, Sonja Burgstaller, Ella Willenbacher, Martin Schalling, Nicole C.C. Them, Pavla Kadlecová, Christoph S. Klade, Richard Greil · 发表于：Blood · 年份：2015 · DOI：10.1182/blood-2015-04-637280 · 被引用次数：193 · 研究领域：Myeloproliferative Neoplasms: Diagnosis and Treatment、Eosinophilic Disorders and Syndromes、Cytokine Signaling Pathways and Interactions

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.