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1799 Ropeginterferon in Low-Risk Patients with Polycythemia Vera

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Ji Yun Lee, MD1, Sung-Eun Lee, MD, PhD2*, Sung-Soo Yoon, M.D., Ph.D.3, Deok-Hwan Yang, MD, PhD4*, Sang Kyun Sohn, MD, PhD5*, Seug Yun Yoon6*, Soo-Mee Bang, MD, PhD1, Gyeong Won Lee7*, Chul Won Choi8*, Yunsuk Choi, MD, PhD9, June-Won Cheong, MD, PhD10 and Young Hoon Park11*

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea, Republic of (South)
2Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea, Republic of (South)
3Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of (South)
4Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea, Republic of (South)
5Kyungpook National University Hospital, Daegu, Korea, Republic of (South)
6Division of Hematology & Medical Oncology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea, Republic of (South)
7Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea, Republic of (South)
8Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic of (South)
9Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Republic of (South)
10Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, Korea, Republic of (South)
11Ewha Womans University Mokdong Hospital, Seoul, Korea, Republic of (South)

Background
Patients with polycythemia vera (PV) are considered low risk for major vascular complications if they are under 60 years old and have no history of thrombosis. Unlike high-risk patients, low-risk patients are typically treated with phlebotomies and aspirin. However, frequent phlebotomies can be inconvenient and may cause side effects due to the required iron depletion. They may also be inadequate in controlling certain symptoms, such as severe pruritus and constitutional symptoms. A recent phase-2 randomized study (Low-PV study) compared Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years with phlebotomy in low-risk PV patients. Ropeg significantly reduced the need for phlebotomy procedures, normalized leucocyte and platelet counts, and resulted in no thrombotic events. It also improved the quality of life for PV patients, addressing concerns about drug tolerability and toxicity. Additionally, Ropeg reduced the JAK2V617F allele burden, potentially lowering the risk of long-term disease progression. However, 22% of patients in the Low-PV study did not respond to treatment, suggesting that the fixed low dose of 100 µg every 2 weeks may not be sufficient for effective treatment.

Aims
The aim of this study is to identify the efficacy and safety of Ropeg in low-risk PV patients with rapid dose escalation (250 → 350 → 500 µg every two weeks).

Methods
This is a sub-analysis of a single-arm, open-label, multicenter study assessing the molecular response to Ropeg administration in PV patients. Eligible participants were adults aged 19 years or older, diagnosed with PV according to the 2016 WHO criteria, who had the JAK2V617F mutation and had an elevated hematocrit (Hct) greater than 45% with the requirement for cytoreductive therapy. The starting dose of Ropeg is 250 µg, which is increased to 350 µg at week 2 and to a maximum dose of 500 µg at week 4, administered as a subcutaneous injection every 2 weeks for up to 48 weeks. The dosage was adjusted from the previous dose for reasons of safety and tolerability. Clinical responses and quantitative JAK2V617F mutation allele burden was assessed every 3 months.

Results
With a data cut-off date of July 23, 2024, out of the total 99 enrolled patients, 50 were low-risk PV patients, and pre-treatment medical data for the year prior to Ropeg administration were available for 40 of them. The median age was 47 years (range, 26-59) and 55.0% were male. If the patients were categorized by hydroxyurea treatment, 22 (55.0%) patients were in the hydroxyurea-naïve group and 18 (45.0%) were in the hydroxyurea-resistant/intolerant group. At 1-year, complete hematologic response and molecular response were 82% and 81% in the hydroxyurea-naïve group and 50% and 41% in the hydroxyurea-resistant/intolerant group, respectively, which was a statistically significant difference. The mean (±SD) number of phlebotomies significantly decreased between the year before Ropeg administration and the year during treatment (3.00±2.43 vs. 0.48±0.68, p < 0.001), regardless of whether the patients were in the hydroxyurea-naïve group (3.45±2.86 vs. 0.41±0.67, p<0.001) or the hydroxyurea-intolerant/resistant group (2.44±1.69 vs. 0.56±0.70, p<0.001). Ropeg treatment over one year showed a statistically significant reduction in JAK2 mutation allele burden. Among a total of 63 treatment-emergent adverse events, 45 cases (40% of patients) were evaluated as treatment-related adverse events (TRAE). The most frequently reported TRAEs were hypertransaminasemia and alopecia. Grade 4 and 5 adverse events were not reported.

Conclusion
These results show that Ropeg could be effective and safe in low-risk PV patients. Ropeg treatment shows effectiveness in reducing phlebotomy frequency and JAK allele burden, with particularly pronounced effects observed in hydroxyurea-naive patients. Based on these findings, treating low-risk PV patients earlier with escalated doses of Ropeg could increase response rates and provide greater long-term benefits.

Disclosures: Yoon: Janssen: Honoraria; F. Hoffmann-La Roche Ltd, Genentech, Inc.: Research Funding; Janssen, Novartis, F. Hoffmann-La Roche Ltd, Genentech, Inc.: Consultancy.

*signifies non-member of ASH