Novel interferon appears safer than HU in PV
Photo by Zak Hubbard
SAN DIEGO—Results of the PROUD-PV trial suggest ropeginterferon alfa-2b is safer than hydroxyurea (HU) for patients with polycythemia vera (PV).
In this phase 3 trial, ropeginterferon alfa-2b demonstrated non-inferiority to HU with regard to complete hematologic response (CHR).
Ropeginterferon alfa-2b also had a significantly better overall safety profile.
Unlike the patients who received HU, none of the patients on ropeginterferon alfa-2b developed secondary malignancies.
Heinz Gisslinger, MD, of the Medical University of Vienna in Austria, presented these results at the 2016 ASH Annual Meeting (abstract 475). The PROUD-PV study was sponsored by AOP Orphan Pharmaceuticals AG.
Dr Gisslinger noted that interferons have been successful in treating PV since the 1980s, although toxicities contribute to discontinuation rates of approximately 25%. Still, interferons are the only known drugs with the potential for disease modification by specific targeting of the malignant clone.
Ropeginterferon alfa-2b is a long-acting, mono-pegylated proline interferon with improved pharmacokinetic properties that allow for administration once every 2 weeks.
The goal of PROUD-PV was to determine how this drug stacks up against HU in both treatment-naive and HU-pretreated patients with PV.
“Our results from the first and largest, prospective, controlled trial of an interferon in polycythemia vera confirm previously reported efficacy,” Dr Gisslinger said.
“The observed safety and tolerability profile of ropeginterferon appears to be superior compared to previously reported data of interferon treatment. The unique disease-modification capability of interferon and its potential to improve progression-free survival hold promise for long-term benefit for patients.”
Patients and treatment
PROUD-PV enrolled 254 patients, and they were randomized to receive ropeginterferon alfa-2b (n=127) or HU (n=127). In both arms, 100% of patients were Caucasian, slightly more than half were female, and the median age was 60 (overall range, 21-85).
The median disease duration was 1.9 months in the ropeginterferon alfa-2b arm and 3.6 months in the HU arm. Thirty-seven percent (n=47) of patients in each arm had previously received HU.
The mean hematocrit was about 50% in both arms, the median spleen length was about 13 cm, about 90% of patients had a normal/slightly enlarged spleen, and the mean JAK2V617F burden was slightly more than 40%.
The median plateau dose was 450 µg in the ropeginterferon alfa-2b arm and 1250 mg in the HU arm.
A quarter (25.2%) of patients had dose reductions due to adverse events (AEs) in the ropeginterferon alfa-2b arm, as did 51.2% of patients in the HU arm. The 12-month discontinuation rate was 16.5% in the ropeginterferon alfa-2b arm and 12.6% in the HU arm.
Response
The study’s primary objective was to demonstrate non-inferiority of ropeginterferon alfa-2b compared to HU. For this, the researchers used the 12-month CHR rate. CHR was defined as normalization of red blood cell, white blood cell, and platelet counts (without phlebotomy).
At 12 months, in the intent-to-treat population, the CHR rate was 43.1% in the ropeginterferon alfa-2b arm and 45.6% in the HU arm (P=0.0028). In the per-protocol population, the CHR rate was 44.3% and 46.5%, respectively (P=0.0036).
The researchers therefore concluded that non-inferiority was demonstrated.
The study’s pre-specified primary endpoint was actually a composite of CHR and spleen length normality. However, this was confounded by the fact that the patients’ median spleen length was almost normal at baseline and the observed change was not clinically relevant.
In the intent-to-treat-population, CHR with spleen normality occurred in 21.3% of patients in the ropeginterferon alfa-2b arm and 27.6% of patients in the HU arm (P=0.2233).
Safety
The incidence of AEs was 81.9% in the ropeginterferon alfa-2b arm and 87.4% in the HU arm. The incidence of grade 3 AEs was 16.5% and 20.5%, respectively. And the incidence of treatment-related AEs was 59.6% and 75.6%, respectively (P<0.05).
