ropeginterferon alfa - 2b versus phlebotomy in low risk patients with polycythemia vera (low–PV study): A multicenter, randomized phase 2 trial

Ropeginterferon Alfa – 2b in Polycythemia Vera (Low–PV Study)

Ropeginterferon Alfa – 2b Versus Phlebotomy in Low Risk Patients with Polycythemia Vera (Low–PV Study): A Multicenter, Randomized Phase 2 Trial

Background
It is not clear whether the addition of interferon to phlebotomy in low risk polycythemia vera patients, can produce superior outcomes.  Investigators attempted to answer this question by designing a phase 2 trial, comparing the addition of ropeginterferon alfa – 2b 2 standard phlebotomy.

Methods
The clinical trial was started in 2017.  Low–PV study was a multicenter open label , parallel group investigator initiated, 2 arm, phase 2 randomized clinical trial which utilized a group sequential adaptive design.  21 hematology centers across Itsly were part of the study.  Patients were recruited consecutively.  Patients had to be at least age 18 but were excluded after the age of 60.  2008–16 World Health Organization criteria for polycythemia vera diagnosis needed to be fulfilled.  Patients were randomized to phlebotomy plus low-dose aspirin or phlebotomy plus low-dose aspirin plus ropeginterferon alfa – 2b.  Patients who were randomized to the standard treatment arm, underwent phlebotomy, 300cc for each phlebotomy session, to maintain hematocrit less than 45%.  Aspirin was dosed at 100 mg daily.  Patients who were randomized to the interferon arm, received  ropeginterferon alfa – 2b subcutaneously at doses of 100 mcg every 2 weeks.  The primary endpoint was treatment response.  Treatment response was defined as a median hematocrit of 45% or lower without progression during 1 year.  The study was powered to meet the threshold difference of 25% difference between the groups, 75% and 50% for the treatment arm versus the standard arm, respectively.  In this article, the second planned interim analysis of 50 patients were recruited, to each group are reported.

Findings
Between February 2, 2017 and March 13, 2020, 146 patients underwent screening.  127 patients were assigned to the standard group or the experimental group, 63 and 64 respectively.  The median follow-up was 12 months.  The second preplanned analysis, already showed a higher response rate in the experimental arm, 84% versus 60%.  The absolute difference of 24%, was within the 95% confidence interval of 7 and 41% while, with a P value of 0.0075.  The Z value, 2.6001, crossed the critical bound of efficacy, 2.5262.  With regards to safety, no statistically significance difference between the groups with regards to the frequency of grade 3 or higher adverse events was seen.  The most common adverse event, neutropenia, was seen in 8% and 4% of treatments respectively.  There were no reported grade 4 grade 5 events. 

Conclusion
The addition of ropeginterferon alfa – 2b to standard phlebotomy and low-dose aspirin, in patients with low risk polycythemia vera, can help maintain hematocrit values at target in a safe manner.

Article Link – Lancet Hematology

https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30373-2/fulltext

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