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

Jin, Jie; Zhang, Lei; Qin, Albert; Wu, Daoxiang; Shao, Zonghong; Bai, Jie; Chen, Suning; Duan, Minghui; Zhou, Huifang; Xu, Ning; Zhang, Sujiang; Zuo, Xuelan; Du, Xin; Wang, Li; Li, Pei; Zhang, Xuhan; Li, Yaning; Zhang, Jingjing; Wang, Wei; Shen, Weihong; Zagrijtschuk, Oleh; Urbanski, Raymond; Sato, Toshiaki; Xiao, Zhijian

doi:10.1186/s40164-023-00415-0

Cited by 12 publications

(17 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We designed a phase II study to primarily evaluate whether initiating ropeginterferon alfa-2b at a higher dose with a simpler and faster intra-patient dose titration, i.e., the 250-350-500 µg dosing regimen, could result in an efficient CHR rate and molecular response (MR) in PV patients at 6 months based on the existing safety data in other indications for ropeginterferon alfa-2b, including viral hepatitis [21][22][23][24][25]. The results demonstrated that a CHR rate of 61.7% was achieved by this dose regimen in 6 months, which was notably higher than previously reported with the slow-titration schema [26]. However, the longer-term efficacy including CHR and MR, safety, and patient discontinuation rate needed to be investigated.…”

Section: Introductionmentioning

confidence: 83%

“…The CHR rates, based on the central laboratory assessments, at 12, 24, 36, and 52 weeks of the treatment were 44.9% [26], 61.2% [26], 69.4%, and 71.4%, respectively. Previously, a CHR rate of 43% following 1 year of treatment with ropeginterferon alfa-2b at the slow-titration schema was reported in the PROUD-PV study [16].…”

Section: Chr Rates Durability and Time To Chrmentioning

confidence: 98%

“…All patients had previ-ously received and had become intolerant to HU treatment according to the ELN criteria [27]. Of the patients, 61.2% had previously received an IFN-based therapy [26]. All patients needed cytoreductive therapy at baseline.…”

Section: Patient Demographics Baseline Characteristics and Dispositionmentioning

confidence: 99%

See 2 more Smart Citations

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment

Suo,

Fu,

Qin

et al. 2024

J Hematol

View full text Add to dashboard Cite

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation.Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2 V617F allelic burden, time to first CHR, and safety assessments. Results:The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2 V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2 V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twentynine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm 2 at baseline to 50.2 cm 2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion:The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

show abstract

Section: Introductionmentioning

confidence: 83%

Section: Chr Rates Durability and Time To Chrmentioning

confidence: 98%

See 1 more Smart Citation

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment

Suo,

Fu,

Qin

et al. 2024

J Hematol

View full text Add to dashboard Cite

show abstract

“…While our experience demonstrates that such combination is feasible and safe, the optimization of ropegIFNα2b use with avoidance of drug underdosing both at therapy start and in case of suboptimal response, could maximize the therapeutic bene t [16]. Indeed, higher doses of ropegIFNα2b recently showed a 61.2% of CHR rate at week 24, with acceptable but not negligible toxicity [17].…”

Section: Discussionmentioning

confidence: 99%

Real-life use of ropeg-interferon α2b in Polycythemia Vera: patient selection and clinical outcomes

Palandri,

Branzanti,

Venturi

et al. 2024

Preprint

View full text Add to dashboard Cite

Background Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. Methods As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Results Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. Conclusions This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

show abstract

“…Interim data from a multicenter study in Korea and a phase II study in China suggest that an accelerated design regimen could be used, and the ECLIPSE-PV and EXCEED-ET Studies are also investigating an optimized dosing regimen (ClinicalTrials.gov Identifier: NCT05481151 and NCT05482971). 52 , 83 Blood counts are monitored every 2 weeks, and HU is tapered down on an individualized basis while the interferon dose is increased. For those on HU prior to initiating ropeginterferon alfa-2b-njft, taper the HU off by reducing the total biweekly HU dose by 20–40% every 2 weeks during weeks 3–12 with complete discontinuation of HU by week 13.…”

Section: Practical Management Of Interferon-based Therapiesmentioning

confidence: 99%

Interferons in the treatment of myeloproliferative neoplasms

Vachhani,

Mascarenhas,

Bose

et al. 2024

Therapeutic Advances in Hematology

View full text Add to dashboard Cite

Interferons are cytokines with immunomodulatory properties and disease-modifying effects that have been used to treat myeloproliferative neoplasms (MPNs) for more than 35 years. The initial use of interferons was limited due to difficulties with administration and a significant toxicity profile. Many of these shortcomings were addressed by covalently binding polyethylene glycol to the interferon structure, which increases the stability, prolongs activity, and reduces immunogenicity of the molecule. In the current therapeutic landscape, pegylated interferons are recommended for use in the treatment of polycythemia vera, essential thrombocythemia, and primary myelofibrosis. We review recent efficacy, molecular response, and safety data for the two available pegylated interferons, peginterferon alfa-2a (Pegasys) and ropeginterferon alfa-2b-njft (BESREMi). The practical management of interferon-based therapies is discussed, along with our opinions on whether to and how to switch from hydroxyurea to one of these therapies. Key topics and questions related to use of interferons, such as their safety and tolerability, the significance of variant allele frequency, advantages of early treatment, and what the future of interferon therapy may look like, will be examined. Pegylated interferons represent an important therapeutic option for patients with MPNs; however, more research is still required to further refine interferon therapy.

show abstract

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

Cited by 12 publications

References 12 publications

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment

Real-life use of ropeg-interferon α2b in Polycythemia Vera: patient selection and clinical outcomes

Interferons in the treatment of myeloproliferative neoplasms

Contact Info

Product

Resources

About