Project description:Myeloproliferative neoplasms (MPN) such as essential thrombocythemia (ET) and polycythemia vera (PV) are rare during pregnancy. However, they are harmful because they are associated with an increased risk of thromboembolic, hemorrhagic, or microcirculatory disturbances or placental dysfunction leading to fetal growth restriction or loss. Low-dose aspirin and low-molecular-weight heparin (LMWH) are recommended to reduce pregnancy complications, and interferon (IFN) is the only treatment option for cytoreductive therapy based on the likelihood of live birth in pregnant women with MPN. Since ropeginterferon alfa-2b is the only available IFN in South Korea, we present a case report of ropeginterferon alfa-2b use during pregnancy in an MPN patient. A 40-year-old woman who had been diagnosed with low-risk PV in 2017 and had been maintained on phlebotomy, hydroxyurea (HU), and anagrelide (ANA) for 4 years was confirmed as 5 weeks pregnant on 9 December 2021. After stopping treatment with HU and ANA, the patient showed a rapid increase in platelet count (1113 × 109/L to 2074 × 109/L, normal range, 150-450 × 109/L) and white blood cell count (21.93 × 109/L to 35.55 × 109/L, normal range, 4.0-10.0 × 109/L). Considering the high risk of complications, aggressive cytoreductive treatment was required, for which we chose ropeginterferon alfa-2b, as it is the only available IFN agent in South Korea. The patient underwent 8 cycles of ropeginterferon alfa-2b over 6 months during pregnancy and delivered without any neonatal or maternal complications. This case report highlights the importance of considering treatment options for MPN patients who are pregnant or planning a pregnancy, as well as the need for further investigation into the safety and efficacy of ropeginterferon alfa-2b in this population.

| S-EPMC10048098 | biostudies-literature

Cost-effectiveness of ropeginterferon alfa-2b-njft for the treatment of polycythemia vera.

Project description:Aim: Patients with polycythemia vera (PV), a rare and chronic blood cancer, are at a higher risk for thromboembolic events, progression to myelofibrosis, and leukemic transformation. In 2021, ropeginterferon alfa-2b-njft (BESREMi®) was approved in the US to treat adults with PV. The purpose of this study is to estimate the cost-effectiveness of ropeginterferon alfa-2b-njft, used as a first- or second-line treatment, for the treatment of patients with PV in the US. Materials & methods: A Markov cohort model was developed from the healthcare system perspective in the United States. Model inputs were informed by the PROUD-PV and CONTINUATION-PV studies and published literature. The model population included both low-risk and high-risk patients with PV. The model compared ropeginterferon alfa-2b-njft used either as first- or second-line versus an alternative treatment pathway of first-line hydroxyurea followed by ruxolitinib. Results: Over the modeled lifetime, ropeginterferon alfa-2b-njft provided an additional 0.4 higher quality-adjusted life years (QALYs) and 0.4 life-years with an added cost of USD60,175, resulting in a cost per QALY of USD141,783. The model was sensitive to treatment costs, the percentage of patients who discontinue hydroxyurea, the percentage of ropeginterferon alfa-2b-njft users who switch to monthly dosing, the percentage of ropeginterferon alfa-2b-njft users as 2nd line treatment, and the treatment response rates. A younger patient age at baseline and a higher percentage of patients with low-risk disease improved the cost-effectiveness of ropeginterferon alfa-2b-njft. Conclusion: Ropeginterferon alfa-2b-njft is a cost-effective treatment option for a broad range of patients with PV, including both low- and high-risk patients and patients with and without prior cytoreductive treatment with hydroxyurea.

| S-EPMC10690394 | biostudies-literature

Ropeginterferon alfa-2b, a novel IFNα-2b, induces high response rates with low toxicity in patients with polycythemia vera.

Project description:In this prospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-pegylated interferon (IFN) α-2b isoform, ropeginterferon alfa-2b. The unique feature of ropeginterferon alfa-2b is a longer elimination half-life, which allows administration every 2 weeks. We present data from 51 polycythemia vera patients. The main goal was to define the maximum tolerated dose and to assess safety and efficacy. A dose range of 50 to 540 µg was tested without the appearance of dose-limiting toxicities. All drug-related adverse events were known toxicities associated with IFN-α. The cumulative overall response rate was 90%, comprising complete response in 47% and partial response in 43% of patients; the best individual molecular response level was a complete response in 21% of patients and partial response in 47%. Notably, we did not observe any correlation between the dose level and the response rate or response duration, suggesting that already low levels of ropeginterferon alfa-2b are sufficient to induce significant hematologic and molecular responses. These data suggest promising efficacy and safety of ropeginterferon alfa-2b and support the development of the drug in a randomized phase 3 clinical trial. The study was disclosed at www.clinicaltrials.gov as #NCT01193699 before including the first patient.

| S-EPMC4608390 | biostudies-literature

Ethnic sensitivity analyses of pharmacokinetics, efficacy and safety in polycythemia vera treatment with ropeginterferon alfa-2b.

Project description:Ropeginterferon alfa-2b (Ropeg) is approved for the treatment of adults with polycythemia vera (PV). This report aims to analyze the ethnic sensitivity of Ropeg for the treatment of PV, comparing the pharmacokinetics (PK), efficacy, and safety profiles across diverse ethnic groups. We conducted a relevant review of PV and analysis of data obtained from clinical studies involving Ropeg. The PK behavior of ropeg showed no significant differences between Chinese and overseas populations. Their efficacy and safety profiles were similar across the ethnic groups. The analyses indicated that the dose-exposure-response profile of Ropeg was consistent irrespective of ethnic variations. The results suggest that Ropeg exhibits a consistent PK and pharmacodynamics profile and a similar therapeutic effect across different ethnic groups, confirming its efficacy and safety in the global treatment of PV. More generally, these findings support the broader application of Ropeg in diverse patient populations and emphasize the need for an inclusive clinical practice.

| S-EPMC11463156 | biostudies-literature

Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo.

Project description:Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation. Recommended treatments include hydroxyurea and interferon-alpha. Several groups have reported a reduction in the JAK2 mutant allele burden in interferon-treated patients, but significance of this observation is questioned. We characterized the activity of ropeginterferon alpha-2b, a novel form of interferon-alpha recently shown to be safe and efficacious in polycythemia vera. Ropeginterferon was able to inhibit the proliferation of the HEL, UKE-1, and UT-7 JAK2-mutant cell lines while sparing JAK2-wild-type UT-7 and normal CD34+ cells growth. In vitro treatment of erythroid progenitors derived from PV patients showed that ropeginterferon could considerably inhibit the growth of endogenous erythroid colonies, a hallmark of polycythemia vera. Finally, we could study in sequential samples the clonal architecture of erythroid progenitors derived from patients included in a randomized study comparing hydroxyurea to ropeginterferon. After 1 year of treatment with ropeginterferon, the ratio of JAK2-mutated to wild-type colonies grown from bone marrow progenitors was reduced by 64%, compared to 25% in patients receiving hydroxyurea. This study shows that ropeginterferon has a potent targeted activity against JAK2-mutant cells and is able to drastically reduce the proportion of malignant progenitors in patients treated with this drug.

| S-EPMC6172224 | biostudies-literature

A new dosing regimen of ropeginterferon alfa-2b is highly effective and tolerable: findings from a phase 2 study in Chinese patients with polycythemia vera.

Project description:Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 μg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 μg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

| S-EPMC10286412 | biostudies-literature

Cost-utility analysis of ropeginterferon alfa-2b to manage low-risk patients with polycythemia vera as compared to phlebotomy only in the Austrian healthcare system.

Project description:Treatment of polycythemia vera (PV) aims to maintain hematocrit on target to reduce risk of thrombotic complications, while preventing disease progression to myelofibrosis (MF) and acute myeloid leukemia (AML). This analysis evaluated cost-effectiveness of adding ropeginterferon alfa-2b (ropegIFNα) to phlebotomy in patients with low-risk PV (those younger than 60 years without prior thrombosis), compared to phlebotomy alone. We combined a 12-month decision tree with a semi-Markov cohort model comparing ropegIFNα to the standard treatment from the Austrian healthcare system perspective over 30 years. Outcomes were quality adjusted life years (QALYs), costs, and incremental cost-utility ratio (ICUR). Model inputs were obtained from the phase 2 Low-PV study, additional published literature and from Austrian-specific cost databases. One-way and probabilistic sensitivity analyses (SA) assessed the robustness of findings. RopegIFNα led to 1,43 higher QALYs and 50.960 EUR overall higher costs compared to phlebotomy alone, with an ICUR of 35.525 EUR/QALY. Thrombosis, MF, and AML costs decreased for the ropegIFNα group by 12%, 30% and 16% respectively, due to the delayed complications onset and disease progression. In the one-way SA, ropegIFNα costs and discount rates had the greatest impact on results. The probabilistic SA showed a 100% probability of cost-effectiveness at willingness-to-pay threshold aligned to the Austrian GDP per capita. RopegIFNα is a cost-effective treatment option for patients with low-risk PV. These findings suggest that early treatment with ropegIFNα could ensure optimal resource allocation by preventing costly thrombotic events and progression to MF whilst increasing patient quality of life.

| S-EPMC11868240 | biostudies-literature

Molecular responses and chromosomal aberrations in patients with polycythemia vera treated with peg-proline-interferon alpha-2b.

Project description:Fifty-one polycythemia vera (PV) patients were enrolled in the phase I/II clinical study PEGINVERA to receive a new formulation of pegylated interferon alpha (peg-proline-IFN?-2b, AOP2014/P1101). Peg-proline-IFN?-2b treatment led to high response rates on both hematologic and molecular levels. Hematologic and molecular responses were achieved for 46 and 18 patients (90 and 35% of the whole cohort), respectively. Although interferon alpha (IFN?) is known to be an effective antineoplastic therapy for a long time, it is currently not well understood which genetic alterations influence therapeutic outcomes. Apart from somatic changes in specific genes, large chromosomal aberrations could impact responses to IFN?. Therefore, we evaluated the interplay of cytogenetic changes and IFN? responses in the PEGINVERA cohort. We performed high-resolution SNP microarrays to analyze chromosomal aberrations prior and during peg-proline-IFN?-2b therapy. Similar numbers and types of chromosomal aberrations in responding and non-responding patients were observed, suggesting that peg-proline-IFN?-2b responses are achieved independently of chromosomal aberrations. Furthermore, complete cytogenetic remissions were accomplished in three patients, of which two showed more than one chromosomal aberration. These results imply that peg-proline-IFN?-2b therapy is an effective drug for PV patients, possibly including patients with complex cytogenetic changes.

| S-EPMC4657499 | biostudies-literature

Ropeginterferon Alfa-2b: Efficacy and Safety in Different Age Groups.

Project description: Not available

| S-EPMC7587416 | biostudies-literature