Ropeginterferon Alfa-2b Demonstrates Long-Term QOL Improvements in Polycythemia Vera

Heinz Gisslinger, MD

Treatment with ropeginterferon alfa-2b-njft (Besremi) induced low symptom burden and low phlebotomy requirement compared with best available treatment in patients with polycythemia vera, according to long-term data from the phase 3 PROUD-PV (NCT01949805) and CONTINUATION-PV (NCT02218047) trials.¹

The findings presented at the 2022 EHA Congress showed that occurrence of symptoms defined in the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) was lower in the sixth year of treatment, compared with the first year from week 4, for 6 of 10 symptoms, including fatigue, early satiety, abdominal discomfort, inactivity, itching, and fevers. Overall, 15.7% of patients who received ropeginterferon alfa-2b reported an occurrence of disease-related symptoms during the sixth year of treatment compared with 20.7% of patients in the control arm. Up to week 4 of treatment in the first year, patient-reported symptoms occurred in 9.5% of all patients.

Additionally, in the sixth year of treatment, 81.4% patients in the experimental arm required no phlebotomies maintain hematocrit below 45% with 60% of patients in the control arm (P = .005).

“Long-term ropeginterferon alfa-2b [therapy] fulfills treatment goals important to patients with polycythemia vera,” lead study author Heinz Gisslinger, MD, a professor and program director for Myeloproliferative Neoplasms at the Medical University of Vienna, said in a presentation of the data.

Ropeginterferon alfa-2b is a monopegylated recombinant interferon alfa-2b with improved pharmacokinetics, allowing for administration every 2 to 4 weeks. In November 2021, the FDA approved ropeginterferon alfa-2b for use as a treatment in patients with polycythemia vera based on findings on safety from the phase 1/2 PEGINVERA trial (NCT01193699) and PROUD/CONTINUATION-PV studies and efficacy findings from the PEGINVERA clinical study program.²

Prior efficacy data from CONTINUATION-PV demonstrated that patients in the ropeginterferon alfa-2b arm (n = 95) achieved a complete hematologic response (CHR) rate of 54.6% compared with 34.9% of patients in the control arm (n = 74; rate ratio [RR], 1.55; 95% CI, 1.07-2.26; P = .02).³ Additionally, patients in the ropeginterferon alfa-2b arm had a 66% molecular response rate vs 19.4% of patients in the control arm (RR, 3.23; 95% CI, 2.01-5.19; P < .0001).

The final analysis after 6 years of treatment assessed the patient-related long-term benefit of ropeginterferon alfa-2b vs best available treatment. PROUD/CONTINUATION-PV enrolled patients with treatment-naïve polycythemia vera and patients pretreated with hydroxyurea (Hydrea) within 3 years who did not achieve a complete response.

Patients were randomized 1:1 in the PROUD-PV trial to receive either subcutaneous ropeginterferon alfa-2b, which was given biweekly at a starting dose of 100 μg, or oral hydroxyurea at a starting daily dose of 500 mg. After 1 year of treatment, 89.6% of patients in the ropeginterferon alfa-2b arm and 68.5% in the hydroxyurea arm rolled over to the CONTINUATION-PV trial for 5 more years of treatment. Patients in the ropeginterferon alfa-2b arm continued treatment, and patients in the control arm received the best available treatment. Patients were stratified by age, prior thromboembolic event, and prior hydroxyurea.

The primary end point of PROUD-PV was establishing noninferiority of ropeginterferon alfa-2b vs hydroxyurea in terms of CHR with normal spleen size at 12 months. The primary objectives of CONTI-PV comprised CHR with normalization of spleen size and improved disease burden regarding splenomegaly, microvascular disturbances, pruritus, and headache.³

Baseline characteristics at screening in PROUD-PV showed that 100% of patients were White and had polycythemia vera confirmed by bone marrow biopsy. The 2 arms had similar median ages (58 years and 57.9 years in the ropeginterferon alfa-2b and control arms, respectively), female patients (50.5% and 52.7%), pretreatment with hydroxyurea (32.6% and 31.1%), mean hematocrit (48.3 and 50.1), spleen length (13.5 cm and 12.8 cm), normal spleen function (41.1% and 48.6%), clinically significant splenomegaly (7.4% and 10.8%), and disease-related symptoms (15.8% and 23%). The median disease duration was 1.8 months (range, 0-146) in the experimental arm and 1.6 months (range, 0-92) in the control arm.

At year 6, 88% of patients in the control arm remained on hydroxyurea as the best available treatment, and the remaining 12% switched to interferon therapy. The median cumulative 4-weekly dose of ropeginterferon alfa-2b was 499 μg (interquartile range [IQR], ±268-782) in the sixth year of treatment. The median dose of hydroxyurea was 1000 mg/day (IQR, 750-1500).

Additional data showed depletion of the JAK2V617F allele burden may lower the risk of progression to secondary myelofibrosis. After 6 years of treatment, JAK2V617F allele burden decreased to less than 1% in 20.7% of patients in the ropeginterferon alfa-2b arm compared with 1.4% in the control arm (P = .0001).

Investigators added that patients in patients in the ropeginterferon alfa-2b arm were significantly more likely to have event-free survival compared with the control arm at a maximum treatment period of 7.3 years (log-rank P = .04).

References

1. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b achieves patient-specific treatment goals in polycythemia vera: final results from the PROUD-PV/CONTINUATION-PV studies. Presented at: 2022 EHA Congress; June 9-12, 2022. Vienna, Austria. Abstract S196.
2. US FDA approves BESREMI (ropeginterferon alfa-2b-njft) as the only interferon for adults with polycythemia vera. News release. PharmaEssentia Corporation. November 12, 2021. Accessed June 13, 2022. https://bwnews.pr/3nbXCYO
3. Gisslinger H, Klade C, Georgiev P, et al. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020;7(3):e196-e208. doi:10.1016/S2352-3026(19)30236-4