Abstract
Background: Polycythemia vera (PV), the most common myeloproliferative neoplasm, is characterized by clonal proliferation of cells from the erythroid, myeloid, and megakaryocytic cells. Ropeginterferon alfa-2b, a long-acting mono-pegylated interferon, has shown promise in improving tolerability and reducing dosing frequency. In the PROUD/CONTINUATION-PV study, achieved sustained complete hematologic response (CHR) and molecular response (MR) with favorable tolerability. However, data on long-term response maintenance and predictive factors are limited.
Aims: This study aimed to evaluate the durability of CHR and MR and identify factors associated with sustained responses in PV patients treated with ropeginterferon alfa-2b.
Methods: In this investigator-initiated, single-arm, open-label phase 2 study conducted at 16 institutions in Korea, PV patients who required cytoreductive therapy were treated with ropeginterferon alfa-2b using a rapid dose-escalation regimen (250→350→500 mcg every 2 weeks for 48 weeks). After initial CHR achievement, dosing intervals were adjusted based on CHR stability. CHR and MR were assessed at regular 12-week intervals through week 108. Maintenance was defined as continuous achievement of CHR or MR from initial response, and loss as any subsequent failure. Kaplan–Meier methods estimated maintenance rates. Univariate and multivariate Cox proportional hazards models identified predictors of response loss.
Results: As of January 3, 2025, 95 patients were enrolled; 77 completed 2-year treatment. The CHR rates were 25 of 94 (26.6%) at 12 weeks, 40 of 87 (46.0%) at 24 weeks, 47 of 84 (56.0%) at 36 weeks, 51 of 81 (63.0%) at 48 weeks, 56 of 77 (72.7%) at 60 weeks, 55 of 77 (71.4%) at 72 weeks, 58 of 77 (75.3%) at 84 weeks, 57 of 77 (74.0%) at 96 weeks, and 63 of 77 (81.8%) at 108 weeks, respectively. Corresponding MR rates were 28 of 88 (31.8%), 29 of 81 (35.8%), 38 of 77 (49.4%), 42 of 74 (56.8%), 52 of 74 (70.3%), 51 of 74 (68.9%), 54 of 74 (73.0%), 56 of 74 (75.7%), 59 of 74 (79.7%). Among 73 patients who achieved CHR at least once, 54 (68.4%) maintained it; among 63 patients who achieved MR at least once with baseline JAK2 V617F allele burden ≥10%, 54 (85.7%) maintained it. In the univariate Cox analysis, longer time to first CHR predicted higher risk of CHR loss (HR 1.01, 95% CI 1.01–1.21, p=0.03), while female showed a lower likelihood of CHR loss compared to male (HR=0.16, 95% CI 0.05-0.57, p=0.004). Additionally, patients with higher baseline alkaline phosphatase (ALP) levels were more prone to sustained CHR than those with lower ALP levels (HR=0.98, 95% CI 0.96-1.00, p=0.04). However, time to first MR did not predict MR loss (HR 1.00, 95% CI 0.88–1.14, p=1.00).Conclusion: This study demonstrates that a rapid dose-escalation strategy of ropeginterferon alfa-2b achieved high rates of both CHR and MR with durable maintenance in patients with PV who required cytoreductive therapy. Notably, earlier achievement of CHR was significantly associated with sustained long-term CHR maintenance, highlighting the importance of prompt therapeutic response from the perspective of the timely treatment optimization. These results underscore the need for treatment strategies that prioritize earlier CHR achievement to ensure durable long-term remission.
