P1, N=15, Not yet recruiting, University of Utah

The PROUD-CONTI study showed the superiority of rIFNα compared to hydroxyurea (HU), which led to the European Medicines Agency approval in 2019 of ropeginterferon alpha-2b ("ropegIFN") for ELN-defined high-risk PV patients. Moreover, as PV progresses, the development of myelofibrosis is the leading cause of morbidity, perhaps abetted by PHLEB-O. Here, we review recent progress in the treatment of PV with rIFNα and discuss our rationales and perspectives for, and the endorsement of the initial treatment with rIFNα of both low and high-risk PV patients, unless a contraindication exists to its use.

Our findings redefine epigenetic regulation in LUAD, demonstrating that regional methylation patterns-not global promoter status-orchestrate oncogene activation. We propose a novel framework for spatially resolved methylomics, advocating 1) dual-target assays monitoring both promoter and gene body methylation to improve diagnostic precision, and 2) therapeutic exploitation of SHOX2's intronic methylome as a druggable epigenetic switch.

NLR half reduction significantly predicted hematologic response (week 24 OR 6.42, p = 0.001) and molecular response consistently across all time points (week 24 OR 27.94, p < 0.001). NLR half reduction is a simple, cost-effective biomarker that may reflect molecular response and treatment efficacy in PV.

The standard treatment is low-dose aspirin and phlebotomy, with cytoreductive therapy added for high-risk PV. All 3 patients achieved and maintained complete hematologic response with reduced JAK2 V617F allele burden. Ropeg-IFN is an effective and safe therapy for elderly patients with PV that also improves quality of life.

The patient maintained CHR and MR for 2 years following treatment discontinuation. We also discuss the potential benefit of ropeg-IFN in low-risk PV patients who were not previously considered candidates for aggressive cytoreductive therapy.

Clinical trials have demonstrated that ropeg-IFN reduces the JAK2 V617F allele burden, which is recognized as an independent risk factor for disease progression and thrombosis, apart from traditional factors such as age and prior cardiovascular events. To improve the prognosis of PV, it is essential to accumulate clinical evidence on trends in JAK2 V617F allele burden and the conditions required to maintain hematologic control after discontinuation of ropeg-IFN therapy in real-world settings.

Ongoing treatment with hydroxyurea was substituted with ropeg (week 0: 250 mcg; week 2: 350 mcg; week 4 onwards: 500 mcg every 2 weeks). In conclusion, ropeg was safe and induced CHCR associated with significant molecular responses in patients with early MF. ClinicalTrials.gov Identifier: NCT04988815.

P2, N=35, Not yet recruiting, Jonsson Comprehensive Cancer Center

P3, N=1301, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Jan 2027

P3, N=1150, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Dec 2025 --> Dec 2026

P4, N=222, Not yet recruiting, Women’s Hospital, Zhejiang University School of Medicine; Women’s Hospital, Zhejiang University School of Medicine