The effect of ropeginterferon alfa-2b on phlebotomy and Hct control in PV: A cross-study analysis

Results from a cross-study analysis of three prospective phase II trials (Japan, NCT04182100; China, NCT05485948; Korea, KCT0006138) evaluating ropeginterferon alfa-2b in 177 patients with polycythemia vera (PV) were published in Leukemia & Lymphoma by Hunter et al. The trials in China and Korea used a higher initial dose and accelerated titration (HIDAT) regimen, while the study in Japan used the slow titration regimen. Key endpoints included phlebotomy-free hematocrit (Hct) response rate, annualized phlebotomy frequency, complete hematologic response (CHR), and JAK2V617F variant allele frequency (VAF) change. 

Key data: The phlebotomy-free Hct response rates were higher in Week 20–32 maintenance vs Week 0–32 (Japan, 79.31% vs 24.14%; China, 75.51% vs 30.61%; Korea, 66.67% vs 44.44%). In Weeks 0–32, higher phlebotomy-free Hct response rates were observed in studies using the HIDAT vs slow titration regimen (38.6% vs 24.1%; p < 0.0001), while the inverse was true in Weeks 20–32 (70.5% vs 79.3%; p < 0.0001). Mean annualized phlebotomy rates were lower in the pooled HIDAT cohort vs the slow titration cohort during Weeks 0–32 (0.37 vs 2.31 per year; p < 0.0001) and Weeks 20–32 (0.13 vs 0.60 per year; p = 0.0218); a greater proportion of patients receiving HIDAT vs slow titration were phlebotomy-free during Weeks 0–32 (86.6% vs 31.0%; p < 0.0001) and Weeks 20–32 (97.3% vs 86.2%; p < 0.0001). HIDAT was also associated with deeper JAK2V617F VAF reductions and higher CHR rates at 12 months. Both regimens were well tolerated, with serious adverse events occurring in 3.4%, 18.4%, and 11.1% of patients in the Japanese, Chinese, and Korean studies, respectively. 

Key learning: Ropeginterferon alfa-2b provided durable Hct control and reduced phlebotomy dependence across a broad PV population, including high-risk patients. The HIDAT regimen was associated with more rapid and sustained phlebotomy-free responses; however, as comparisons are indirect and non-randomized, results should be interpreted with caution.