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Clinical Trial
. 2015 Oct 8;126(15):1762-9.
doi: 10.1182/blood-2015-04-637280. Epub 2015 Aug 10.

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

Heinz Gisslinger  1 , Oleh Zagrijtschuk  2 , Veronika Buxhofer-Ausch  3 , Josef Thaler  4 , Ernst Schloegl  5 , Guenther A Gastl  6 , Dominik Wolf  7 , Robert Kralovics  8 , Bettina Gisslinger  1 , Karin Strecker  9 , Alexander Egle  10 , Thomas Melchardt  10 , Sonja Burgstaller  4 , Ella Willenbacher  6 , Martin Schalling  1 , Nicole C Them  11 , Pavla Kadlecova  12 , Christoph Klade  2 , Richard Greil  10
Affiliations
Clinical Trial

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

Heinz Gisslinger et al. Blood. .

Abstract

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.

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Figures

Figure 1
Figure 1
Hematologic response over time in the study.
Figure 2
Figure 2
Kaplan-Meier estimates of complete hematologic response, any response, and best individual hematologic response in the study (according to ELN 2009, see “Methods”).
Figure 3
Figure 3
JAK2 molecular response in the study. (A) JAK2 allelic burden in the whole study population. (B) Molecular responses (rates) in patients with at least 20% JAK2 allelic burden at baseline.
Figure 4
Figure 4
JAK2 allelic burden for each patient (baseline allelic burden ≥20%), comparing the best individual response with baseline.
Figure 5
Figure 5
Adverse events occurrence over time, shown separately for drug-related AEs (according to investigators) and adjusted for the number of patients exposed per period.
See this image and copyright information in PMC

References

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