Distinct Factors Influence on Complete Hematological Response Maintenance in Polycythemia Vera Patients Treated with Ropeginterferon Alfa-2b: From a Phase 2 Study in South Korea
Authors: Lee Sung-Eun , Yoon Sung-Soo , Yang Deok-Hwan , Lee Gyeong Won , Yoon Seug Yun , Sohn Sang Kyun , Shin Ho-Jin , Bae Sung Hwa , Choi Chul Won , Choi Yunsuk , Cheong June-won , Bang Soo-Mee , Park Joon Seong , Oh Sukjoong , Park Yong , Park Young Hoon 
Published: December 2024

Background: Polycythemia Vera (PV) is the most prevalent myeloproliferative neoplasm, characterized by the clonal proliferation of erythroid, myeloid, and megakaryocytic cells. Ropeginterferon alfa-2b, a monopegylated interferon-a with an extended half-life, has shown promise in reducing dosing frequency while improving safety and patient compliance. Open-label, randomized phase III studies (PROUD/CONTINUATION-PV) demonstrated that starting with 50 or 100 mcg every 2 weeks, with dose increases of 50 mcg up to 500 mcg, ropeginterferon alfa-2b effectively achieves durable complete hematological response (CHR) and is well tolerated long-term. Recently, we reported one-year results from the phase 2 study in South Korea, using a dosing schedule of 250-350-500 mcg, escalated every 2 weeks until 48 weeks. However, limited data exist on the factors for maintaining CHR, including dose schedule.

Aims: This study aims to evaluate the maintenance rate of CHR in patients who initially achieved it, compare patient characteristics between those who maintained CHR and those who did not, and assess the factors influencing the CHR maintenance

Methods: In phase 2, single-arm, open-label, investigator-initiated trial at 16 sites in South Korea, patients were treated with a simplified dosing schedule of 250-350-500 mcg, escalated every 2 weeks until 48 weeks, and then adjusting dose interval in patients with stable responses who achieve CHR at least once. Maintenance is defined as sustained CHR from the first visit where CHR was achieved. CHR maintenance was assessed at follow-up visits until 96 weeks, based on data cut-off on June 14, 2024. The study identifies the first assessment visit where CHR was achieved and evaluates CHR maintenance until the last assessment visit. Maintenance loss is defined if CHR was lost at any subsequent visit. The proportion of patients who maintained CHR over the 96-week period was calculated. In addition, the factors influencing the CHR maintenance including the cumulative dose and dosing interval were analyzed using a Cox proportional hazard model.

Results: As of the cut-off date of June 14, 2024, 60 out of 95 patients had completed 96 weeks (full analysis set). The median age was 56 years (Q1-Q3, 46-63), with 36 (60%) male. Among the patients, 25 (42%) had high-risk PV, and 26 (43%) were resistant or intolerant to hydroxyurea. The median disease duration was 857 days (Q1-Q3, 352-1,850). Of the 60 patients, 9 (15%) never achieved CHR, while 51 (85%) achieved CHR at least once within 96 weeks. In patients who achieved CHR, the change in JAK2 V617F allele burden from baseline to the first CHR was -19% (Q1-Q3, -34 to -11). The cumulative dose of ropeginterferon to reach the first CHR was 5,600 mcg (Q1-Q3, 2,600-8,600). Regarding dose intervals, 11 (22%) maintained the same interval, and 40 (78%) increased the interval.

Among the 51 patients who achieved CHR, 68.6% (35/51) maintained CHR consistently, and 31.4% (16/51) experienced CHR loss after their first CHR achievement. Increasing the dose interval (to 3 or 4 weeks) compared to maintaining the same interval (2 weeks) did not significantly impact the risk of CHR maintenance loss (hazard ratio [HR]=0.51 [95% CI, 0.18-1.47], p=0.214). However, the risk of CHR maintenance loss increased in patients who consumed alcohol compared to those who never drank (HR=4.73 [95% CI, 1.25-17.90], p=0.022). Similarly, smokers had a higher risk of CHR maintenance loss compared to non-smokers (HR=4.27 [95% CI, 1.15-15.84], p=0.03). Male patients had an increased risk of CHR maintenance loss compared to female patients (HR=4.56 [95% CI, 1.30-16.05], p=0.018).

Conclusion: These findings highlight the effectiveness of ropeginterferon alfa-2b in achieving and maintaining higher rates of complete hematological response (CHR) in Polycythemia Vera patients. The data demonstrate that the risk of losing CHR remains low even with adjustments to the dosing interval. This supports the conclusion that ropeginterferon alfa-2b is highly effective in sustaining CHR, and that flexibility in dosing intervals does not undermine long-term treatment success.