Besremi (ropeginterferon alfa-2b-njft)

P3, N=426, Not yet recruiting, Incyte Corporation

Modern treatment approaches, including therapeutic phlebotomy, low-dose aspirin, and cytoreductive therapies (hydroxyurea, interferon-α formulations, and ruxolitinib), have reduced blood cell counts and thrombotic risk, yet concerns about treatment-associated cardiovascular toxicity have emerged. Recent cardio-oncology guidelines emphasize structured monitoring for cancer therapy-related cardiovascular toxicity. This mini review summarizes the cardiovascular burden of PV, therapeutic strategies to mitigate risk, and emerging perspectives on cardiotoxicity-including a recently reported case of reversible left ventricular dysfunction associated with ropeginterferon α-2b.

Phase III data from PROUD-PV (NCT01949805; EudraCT, 2012-005259-18) and its phase IIIb extension, CONTINUATION-PV (NCT02218047; EudraCT, 2014-001357-17), demonstrate that ropeg, compared with hydroxyurea, achieves hematologic response more slowly but provides greater, more durable responses after ∼18 months, underscoring the importance of long-term adherence. Early adverse events can challenge adherence, emphasizing the need for proactive symptom management. This review offers evidence- and experience-based perspectives on long-term ropeg treatment and adverse event management to support adherence and maximize therapeutic benefit in PV.

P2, N=35, Not yet recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Mar 2032 --> Sep 2032 | Initiation date: Mar 2026 --> Sep 2026 | Trial primary completion date: Mar 2031 --> Sep 2031

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.

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.

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.

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.

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.

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