P1042: comparison of the response to ropeginterferon alfa-2b in hydroxyurea naïve versus resistance/intolerance polycythemia vera: the korean single-arm, open-label multicenter study

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Hydroxyurea (HU) has been widely used as one of myelosuppressive agents of first choice for polycythemia vera (PV) patients who require cytoreductive therapy by the ELN and NCCN consensus. Although HU minimizes thrombosis risk by achieving a rapid hematologic response, HU treatment can be associated with cytopenia and often unsatisfactory hematological control over time, aphthous and leg ulcers, and concern for the second primary malignancy. Recently, ropeginterferon alfa-2b was developed and an open-label, randomized phase 3 study showed it was more effective in achieving durable hematological and molecular remissions than HU and well tolerated during long-term resistance and intolerance (R/I). Therefore, there are limited data on the clinical efficacy and safety to HU resistance and intolerance patients during ropeginterferon alfa-2b. Aims: We evaluated the clinical efficacy and safety of ropeginterferon alfa-2b in Korrean patients. Additionally, we explored a comparison between HU-naïve and HU-R/I patients to determine whether there are any differences. Methods: This study has been conducted in 16 hospitals in Korea. Eligible patients were 19 years or older with PV diagnosed according to the WHO’s 2016 criteria, requiring cytoreductive therapy and having an elevated hematocrit (hematocrit <45%). Patients were treated with ropeginterferon alfa-2b subcutaneously every 2 weeks, starting with a dose of 250 mcg, followed by 350 mcg at week2, 500 mcg at week 4, and thereafter until week 48. The quantitative JAK2 Val617Phe allele burden was assessed every 3 months. HU resistance and intolerance were defined based on the modified ELN criteria Results: With a data cut-off data of 3 Feb 2023, a total of 99 patients were enrolled, and these analyses were performed in 95 patients in the full analysis set, including 52 (54.7%) patients who were HU-naïve and 42 (45.3%) patients who were HU-R/I. There was no difference between HU-naïve and HU-R/I patients in terms of basic characteristics. Until the cut-off date, 93, 77, 48, and 28 patients were evaluable at 3, 6, 9, and 12 months, respectively. During the dose escalation period, 4 patients (4.5%, 4/88) could not reach 500 mcg due to adverse events, but no serious adverse event was reported. At baseline, the mean Hematocrit (%) was 50.25 ± 5.11, which significantly decreased to 41.14 ± 6.05 at 12 months, respectively. A statistical difference was shown between HU-naive and HU-R/I patients until 36 weeks of treatment, but hematocrit was controlled below 45% after 36 weeks regardless of subgroup. Complete hematologic response (CHR) was achieved in 25 (27%) of 93, 35 (45%) of 77 patients, 31 (65%) of 48 patients, and 18 (64%) of 28 patients at 3, 6, 9, and 12 months, respectively. In subgroup analysis, CHR at 48 weeks was achieved in 11(65%) of 17 HU-naïve and 7 (64%) of 11 HU-R/I patients. Regarding subgroup analysis for the JAK2 Val617Phe allele burden changes, which were analyzed with available samples so far, a trend for a rapid decreasing pattern was shown in HU-naïve patients compared with HU-R/I patients. Summary/Conclusion: Our data demonstrated that ropeginterferon alfa-2b therapy, with rapid dose optimization, induced hematological response, reduced JAK2Val617Phe allele burden, and was well tolerated in Korean patients. Moreover, Compared to HU naïve vs R/I, H-R/I patients showed a delayed CHR response, but not much difference in after 36 weeks of treatment. These results suggest that ropeginterferon alfa-2b is an effective treatment option for PV regardless of prior HU therapy. Keywords: Myeloproliferative disorder, Polycythemia vera