P3, N=1673, Active, not recruiting, National Cancer Institute (NCI)

The propositus was not controlled by hydroxyurea, and JAK2 inhibitors were not tolerated; however, Ropeginterferon-alfa-2b (Ropeg-IFN-α) induced a remission. We report dominantly inherited erythrocytosis secondary to a novel germline JAK2R715T gain-of-function mutation with many but not all comparable molecular features to JAK2V617F PV. We also document a previously unreported inhibitory mechanism of JAK2 signaling by Ropeg-IFN-α.

P3, N=134, Completed, National Taiwan University Hospital | Active, not recruiting --> Completed

Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.

P2, N=49, Active, not recruiting, PharmaEssentia | Trial completion date: Apr 2024 --> May 2025

P2, N=88, Active, not recruiting, National Cancer Institute (NCI)

Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.

P4, N=110, Not yet recruiting, PharmaEssentia

A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

In addition, the chimeric form had reduced cytotoxicity towards Vero cells and increased cell viability under viral load conditions compared with commercial IFN-a2b preparations. Analysis of the pharmacokinetic profile of ryIFN-ApoA-I after a single subcutaneous injection in mice showed a 1.8-fold increased half-life of the chimeric protein compared with ryIFN.

Side effects were observed in one patient (6.2%). Our experience is in support of previous studies regarding ropeginterferon alfa-2b efficacy and safety profile in the treatment of young patients with Ph- MPNs.

P3, N=1345, Active, not recruiting, National Cancer Institute (NCI)

P4, N=480, Recruiting, The First Affiliated Hospital of Medical College of Zhejiang University; The First Affiliated Hospital of Medical College of Zhejiang University | Phase classification: P3 --> P4 | N=320 --> 480

Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis...Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included...General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.

Background: Prior to the approval of ropeginterferon alfa-2b-njft (ropeginterferon) in November 2021, the alternatives to hydroxyurea for the treatment of polycythemia vera (PV) included Janus Kinase inhibitors (JAKi) and older versions of recombinant interferon-alpha (rIFNα). This study examined FAERS reports to detect disproportional reporting odds of drug-associated AEs severity and SOCs in four PV treatments: ropeginterferon, ruxolitinib, interferon alfa-2a, and pacritinib. Ropeginterferon had a significant ROR for non-serious AEs. Peginterferon alfa-2a demonstrated a significant ROR for SAEs.

P3, N=174, Active, not recruiting, PharmaEssentia | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Nov 2024

P1, N=90, Recruiting, Mongolian National University of Medical Sciences

No abstract available

In essential thrombocythemia, ropeginterferon alfa-2b is being evaluated, as are therapies to modify epigenetics and inhibit CALR. The enhanced focus on MPNs brings hope that our field can improve morbidity and mortality in this group of diseases.

Ropeginterferon alfa-2b(P1101) showed it was more effective in achieving durable hematological and molecular remissions than hydroxyurea and well tolerated during long-term application. The updated data showed consistent results with the previous 2022 ASH meeting abstract that ropeginterferon alfa-2b therapy, with rapid dose optimization, induced hematological response, reduced JAK2 allele burden, and was well tolerated in Korean patients. Moreover, we clarified the association between efficacy and MR as assessed by reduction in JAK2 allele burden. More data will be updated during the meeting.

These observations indicate that TYK2 is essential for the effects of IFN-α on HSCs. These results indicate that TYK2 is indispensable for the effects of IFN-α on improvement of MPN features.

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. 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. 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.

Our experience with ropeginterferon alfa-2b further confirms its effectiveness and supports the necessity to expand its use in the treatment of young high-risk patients with ET and PMF.

CASE PRESENTATION: An 81-year-old female with a history of unprovoked DVT/PE on rivaroxaban presented to ED with progressive dyspnea on exertion for four months, a recent fever with a nonproductive cough, night sweats, and two subcutaneous nodules on her low back...These findings favored lupus panniculitis with a negative rheumatological workup, and a low dose of hydroxychloroquine was empirically started...The patient was started on R-CHOP... Though rare, lymphomatoid granulomatosis should be suspected for multiple pulmonary and cutaneous nodules, even in immunocompetent patients.

Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA) and IL-2 (Proleukin), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials...In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.

P1/2, N=15, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Jul 2025 | Trial primary completion date: Jul 2023 --> Jul 2025

Recurrence was not detected in any of the groups after one year follow up. Intralesional IFN-α 2b injection is an appropriate treatment choice for BCC.

P1, N=9, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Feb 2024 --> Feb 2023

No abstract available

GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.

In summary, the use of genetic polymorphisms (specifically ITPA SNPs) to predict efficacy and adverse events inour MPN patients treated with ROPEG shows promise in improving personalized treatment and patient outcomes. Approximately half of patients achieved MMR of JAK2 V617F and loss of co-existing mutations could occur in a subset of MPN patients following ROPEG therapy. Ropeg-Interferon, Single nucleotide polymorphism, Myeloproliferative disorder, Polycythemia vera

Interferon alfa-2b is efficacious for treating low-grade lymphomatoid granulomatosis and hence reducing progression to high-grade disease, whereas patients with high-grade lymphomatoid granulomatosis showed expected responses to chemotherapy. Uncontrolled immune regulation of Epstein-Barr virus is hypothesised to result in the emergence of low-grade disease after chemotherapy, for which treatment with interferon alfa-2b is efficacious.

Although hydroxyurea (HU) remains the myelosuppressive agent of first choice, HU treatment can be associated with cytopenia and often unsatisfactory hematological control over time, aphthous and leg ulcers, and concern for the second primary malignancy. Moreover, rapid dose optimization resulted in achieving adequate hematologic response rapidly without specific adverse reaction during dose escalation, suggesting that this method may be feasible for the patients with polycythemia vera and elevated hematocrit. Keyword : Polycythemia vera, Ropeginterferon alfa-2b, Complete hematologic response, Molecular response, JAK2 Val617Phe allele burden

P3, N=214, Completed, Philipps University Marburg Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Dec 2022

P1, N=9, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=24 --> 9 | Trial completion date: May 2023 --> Feb 2024

P1/2, N=64, Suspended, Roswell Park Cancer Institute | Recruiting --> Suspended

Later, pegylated IFN-α2a (Pegasys) and pegylated IFN-α2b (PegIntron) were introduced, which have since been reported to be better tolerated due to reduced toxicity...Within the hematological malignancies, rIFN-α2 has been used off-label for decades in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs)-i.e., essential thrombocythemia, polycythemia vera, and myelofibrosis-and in recent years rIFN-α2 has been revived with the marketing of ropeginterferon-α2b (Besremi) for the treatment of polycythemia vera patients...Another rIFN formulation-recombinant interferon-β (rIFN-β)-has been used for decades in the treatment of multiple sclerosis but has never been studied as a potential agent to be used in patients with MPNs, although several studies and reviews have repeatedly described rIFN-β as an effective anticancer agent as well. In this paper, we describe the rationales and perspectives for launching studies on the safety and efficacy of rIFN-β in patients with MPNs.

Although hydroxyurea (HU) remains the myelosuppressive agent of first choice, HU treatment can be associated with cytopenias and often unsatisfactory hematological control over time, aphthous and leg ulcers, and concern for the second primary malignancy. Our data demonstrated that ropeginterferon alfa-2b therapy with rapid dose optimization induced hematological response and reduction of JAK2 Val617Phe allele burden, and was well tolerated in Korean patients with polycythemia vera and elevated hematocrit. Updated data with longer follow-up will be presented in the meeting.