Treatment Of Vera Research Articles

Chinese guideline for the diagnosis and treatment of polycythemia vera (2022)

Chinese guideline for the diagnosis and treatment of polycythemia vera (2022)

S196: ROPEGINTERFERON ALFA-2B ACHIEVES PATIENT-SPECIFIC TREATMENT GOALS IN POLYCYTHEMIA VERA: FINAL RESULTS FROM THE PROUD-PV/CONTINUATION-PV STUDIES

Background: Treatment of polycythemia vera (PV) aims to prevent thromboembolic complications, reduce the risk of progression to acute leukemia or myelofibrosis - of particular concern to patients - and ameliorate the symptom burden; specifically, to improve quality of life, therapy should address the most clinically important symptoms while reducing phlebotomies to avoid iron-deficiency symptoms. Long-term efficacy and safety of ropeginterferon alfa-2b have been demonstrated in PROUD-PV/CONTINUATION-PV; the final analysis applied a patient-focused approach. Aims: To analyze the patient-relevant benefit of ropeginterferon alfa-2b versus hydroxyurea (HU)/best available treatment (BAT) over 6 years. Methods: Patients diagnosed with PV according to WHO 2008 criteria who were cytoreduction-naïve or hydroxyurea pre-treated and gave written informed consent were randomized 1:1 to ropeginterferon alpha-2b or control treatment (HU) for one year in PROUD-PV. In CONTINUATION-PV, control arm patients could switch from HU to BAT. Patient-reported PV symptom burden was assessed based on adverse events documented in the patient diary and recorded at each visit; items defined in the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; fatigue, concentration problems, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers) and medical synonyms were evaluated post-hoc. Efficacy assessments included Kaplan-Meier analysis of event-free survival, phlebotomy need and JAK2V617F allele burden. Analyses were conducted on the CONTINUATION-PV full analysis set over 6 years of treatment. Results: The full analysis set comprised 95 patients in the ropeginterferon alfa-2b arm and 74 in the control arm. Patient-reported symptoms defined in the MPN-SAF TSS were present in a small minority (9.5%) of patients per arm at baseline (up to Week 4 of treatment) in this early-stage PV population. Occurrence of the defined symptoms remained low over long-term treatment, reported in 15.7% of patients in the ropeginterferon alfa-2b arm and 20.7% in the control arm during the 6th year of treatment. No phlebotomies were required to maintain hematocrit <45% in the 6th year of treatment in 81.4% of patients receiving ropeginterferon alfa-2b compared with 60.0% of patients in the control arm (p=0.005). Depletion of the JAK2V617F alle burden, which may lower the risk of progression to myelofibrosis, was observed in ropeginterferon alfa-2b treated patients; JAK2V617F allele burden <1% at 6 years was achieved in 19/92 (20.7%) patients in the ropeginterferon alfa-2b arm with baseline allele burden >10%. One patient met this threshold in the control arm (1/70 [1.4%]; p=0.0001). Event-free survival (risk events: disease progression, death and thromboembolic events) over ≥6 years of treatment was significantly higher among ropeginterferon alfa-2b treated patients than the control group (risk events reported in 5/95 vs. 12/74 patients, respectively; p=0.04 [Log-Rank]; Fig 1). Image:Summary/Conclusion: Long-term ropeginterferon alfa-2b therapy fulfils treatment goals important to patients with PV: a good quality of life as indicated by a low symptom burden and phlebotomy requirement, the potential to influence myelofibrosis risk, and better event-free survival versus BAT.

Novel Pegylated Interferon for the Treatment of Chronic Viral Hepatitis.

Ropeginterferon alfa-2b is a novel mono-pegylated and extra-long-acting interferon, being developed for the treatment of myeloproliferative neoplasm (MPN) and chronic viral hepatitis. It has a favorable pharmacokinetic profile and less frequent dosing schedule, i.e., once every two to four weeks, compared to conventional pegylated interferon products, which have multiple isomers and are administered weekly. It was approved for the long-term treatment of polycythemia vera, an MPN, and has been included in the NCCN clinical practice guidelines for this indication. Ropeginterferon alfa-2b has demonstrated efficacy and showed a favorable safety profile for the treatment of chronic viral hepatitis in several clinical studies. In this article, we review its pharmacokinetics and available clinical data and suggest that ropeginterferon alfa-2b administered once every two weeks can serve as a new treatment option for patients with chronic viral hepatitis, including chronic hepatitis B, C, and D.

Bomedemstat tosylate. Lysine-specific demethylase 1 inhibitor, Treatment of essential thrombocythemia, Treatment of polycythemia vera, Treatment of myelofibrosis

Bomedemstat tosylate. Lysine-specific demethylase 1 inhibitor, Treatment of essential thrombocythemia, Treatment of polycythemia vera, Treatment of myelofibrosis

Effect of Aloe vera (Barbadensis Mill) on Letrozole Induced Polycystic Ovarian Syndrome in Swiss Albino Mice.

ABSTRACTBackground:Polycystic ovarian syndrome (PCOS) is the predominant endocrine abnormality in premenopausal women characterised by hyperandrogenism, ovulatory dysfunction, metabolic disturbances such as, insulin resistance and obesity.Aim:The key objective of this study was to evaluate the efficacy of Aloe vera as a treatment drug to identify the factors among female Swiss albino mice (PCOS) models displaying ovarian and metabolic abnormalities and serum sex steroids that are associated with insulin sensitivity.Study Setting and Design:The laboratory breed 4 months adult virgin female Swiss albino mice showing regular estrous cycle and weighing about 20–30 g were employed in present study under CPCSEA guidelines with ethical clearance from the institutional ethical committee. These mice were categorized into two groups with 10 mice in each as control and test animals.Materials and Methods:The mice which were categorised into two groups with 10 mice in each. Carboxy methyl cellulose control and letrozole were induced for 21 days followed by 30 days treatment with distilled water for control, Diane as standard drug and Aloe vera gel formulation. Body weight, estrous cycle, biochemical estimations, hormone assay and histopathology were the parameters studied.Statistical Analysis:IBM SPSS version 20.0 was used for the mean and standard error calculations of biochemical and antioxidants estimation.Results:During the induction period, we observed a significant increase in the body weight, decrease in the number of estrous cycle, and the concomitant increase in diestrous. The biochemical estimations showed changes in the regular activity; hormonal imbalance was observed in hormone assay and cyst formation was also observed in the histopathological study. After the treatment of Aloe vera and Diane, all the parameters showed considerable good results.Conclusion:The findings of the current study provide a baseline data for designing further investigations on the therapeutic benefits of Aloe vera as an adjunct therapy in the management of PCOS.

Immune Dysregulation and Infectious Complications in MPN Patients Treated With JAK Inhibitors

BCR-ABL1-negative myeloproliferative neoplasms are burdened by a reduced life expectancy mostly due to an increased risk of thrombo-hemorrhagic events, fibrotic progression/leukemic evolution, and infectious complications. In these clonal myeloid malignancies, JAK2V617F is the main driver mutation, leading to an aberrant activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Therefore, its inhibition represents an attractive therapeutic strategy for these disorders. Several JAK inhibitors have entered clinical trials, including ruxolitinib, the first JAK1/2 inhibitor to become commercially available for the treatment of myelofibrosis and polycythemia vera. Due to interference with the JAK-STAT pathway, JAK inhibitors affect several components of the innate and adaptive immune systems such as dendritic cells, natural killer cells, T helper cells, and regulatory T cells. Therefore, even though the clinical use of these drugs in MPN patients has led to a dramatic improvement of symptoms control, organ involvement, and quality of life, JAK inhibitors–related loss of function in JAK-STAT signaling pathway can be a cause of different adverse events, including those related to a condition of immune suppression or deficiency. This review article will provide a comprehensive overview of the current knowledge on JAK inhibitors’ effects on immune cells as well as their clinical consequences, particularly with regards to infectious complications.

Treatment of Ropeginterferon Alpha-2b Achieves Hematologic Remission and Molecular Response in Patients with Hydroxyurea- and/or Anagrelide-Resistant/Intolerant Myeloproliferative Neoplasms

▪Background:Ropeginterferon alpha-2b (Ropeg) is a novel pegylated interferon-alpha approved for the treatment of polycythemia vera (PV) in Europe and Taiwan. Prior to its approval in Taiwan, the major options for patients with myeloproliferative neoplasms (MPNs) included hydroxyurea (HU) and/or anagrelide. Patients who are HU/anagrelide resistant/intolerant have limited options, as ruxolitinib is not subsidized by the national health insurance in Taiwan for PV. In 2017, the manufacturer provided a compassionate use program (CUP) for patients who were HU and/or anagrelide resistant/intolerant. Herein, we assessed the efficacy and safety of Ropeg in 20 MPN patients.Methods:To be eligible, patients must be resistant or intolerant to currently available therapies for MPN in Taiwan, mainly HU and anagrelide. Patients with autoimmune disorders, psychiatric illness, and acute/chronic infections were excluded. An accelerated dosing regimen was used, starting from 250 µg, and increased by 100 µg every two weeks until it reached the target dose of 500 µg, if no self-reported discomforts or abnormalities in biochemical or hematological profiles were observed. Efficacy assessments included hematologic parameters, phlebotomy need, and JAK2V617F allele burden. Hematologic remission was defined as platelets ≤400 x 10^9/L and white blood cells <9.5 x 10^9/L for essential thrombocythemia (ET), and platelets ≤400 x 10^9/L, white blood cells <10 x 10^9/L, and hematocrit <45% with no phlebotomy in the past 3 months for PV. Molecular response was defined as a reduction in JAK2V617F allele burden of at least 50% from baseline if baseline value was less than 50%, and a reduction of at least 25% from baseline if the baseline level was at least 50%. Each case was independently reviewed and approved for the use of Ropeg by both Institutional Review Board and the Ministry of Health and Welfare in Taiwan.Results:A total of 20 patients received treatment, which included 14 PV, 4 ET, 1 post-ET myelofibrosis (MF), and 1 pre-fibrotic primary MF (Table 1). There were 12 female and 8 male patients with a median age of 56.1 years old. Of these 20 patients, 18 had JAK2V617F mutation and 5 had a history of thrombosis. Of the 18 ET and PV patients, 13 achieved hematologic remission. The ET patients seemed to achieve hematologic remission faster than PV patients (19.3 vs. 33.2 weeks). Of the 18 patients with JAK2V617F mutation, 7 PV patients and 1 post-ET MF patient achieved molecular response, which took a median of 46 weeks after Ropeg treatment. Reduction in JAK2V617F allele burden was observed in 12 patients. One MF patient discontinued treatment due to disease progression. Another PV patient discontinued treatment due to acute myeloid leukemia transformation, although after treatment, the patient returned to PV state and continued Ropeg treatment. Overall, the drug was well tolerated, as most of the treatment-related adverse events (AEs) were mild to moderate. The AE profile was consistent with those from the phase 3 PROUD/CONTI-PV study. There were no unbearable side effects that led to treatment discontinuation.Conclusion:Our study provided evidence in the efficacy and safety of Ropeg for the treatment of HU-/anagrelide-resistant/intolerant MPNs. Hematologic remission was observed in ET and PV patients, whereas molecular response was observed in only PV patients, possibly due to the small sample size of ET patients. Our experience with Ropeg suggests it to be a promising option for the treatment of MPNs with drug-resistance/intolerance. [Display omitted] DisclosuresChen: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen, Celgene, Novartis, and Panco Healthcare: Honoraria. Shih: PharmaEssentia Co: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene Ltd: Research Funding; Ltd: Research Funding; Novartis: Research Funding. OffLabel Disclosure:Ropeginterferon alfa-2b is a novel interferon alpha indicated for the treatment of polycythemia vera in Europe and in Taiwan. This abstract describes the use of this agent for the treatment of myeloproliferative neoplasm patients with hydroxyurea/anagrelide resistance/intolerance.

Rusfertide (PTG-300) Induction Therapy Rapidly Achieves Hematocrit Control in Polycythemia Vera Patients without the Need for Therapeutic Phlebotomy

▪Background. Polycythemia (PV) patients with hematocrit above 45% are at increased risk of thrombotic complications and are treated with phlebotomy and/or cytoreductive therapy to reach a hematocrit target below 45%. Rusfertide (PTG-300) is a peptidic mimetic of hepcidin that is being developed for treatment of polycythemia vera (PV). A Phase 2 trial has indicated that rusfertide is effective at reducing the number of phlebotomies and maintaining hematocrit below 45% without phlebotomy in PV patients who are either high-risk or low-risk, patients treated with cytoreductive therapy (hydroxyurea, interferon, ruxolitinib) and patients treated with phlebotomy alone (Kremyanskaya, ASH 2020). The current trial (PTG-300-08) tested the ability of rusfertide to normalize hematocrit in PV patients with elevated hematocrit without instituting phlebotomy treatment to normalize hematocrit to below 45% in PV patients without requiring phlebotomy and/or cytoreductive treatment.Methods. Eligible study subjects were diagnosed with PV (in accordance with the WHO 2016 criteria), had baseline hematocrit above 48%, and a history of 3 or more hematocrit values above 48% in the year prior to enrollment. High-risk and low-risk subjects treated with phlebotomy alone or with concurrent cytoreductive therapy were eligible. Rusfertide was added on to each subject's current therapy. The initial rusfertide dose was 40 mg administered subcutaneously twice weekly. When each subject's hematocrit was below 45%, the dosing schedule was changed to weekly and the rusfertide dose was adjusted to maintain hematocrit below 45%.Results. Sixteen subjects (12 male and 4 females) have been enrolled. The mean age is 56.1 years; the mean time since diagnosis is 3.74 years; 10 subjects are low risk PV; 12 subjects are receiving concurrent hydroxyurea and 4 subjects were not receiving cytoreductive therapy. Baseline values (mean, min-max) HCT (51.0%, 47.4 - 59), WBC (12,338/µL, 7,000 - 24,600), RBCs (5.9x10 6/µL, 4.3 - 7.6), platelets (486,500/µL, 242,000 - 904,000). All subjects had rapid decreases in hematocrit to below 45% without the use of phlebotomy (Figure 1a). Hematocrit levels remained well controlled after falling below 45% as investigators reduced rusfertide dose to maintenance once weekly regimen. Hemoglobin (Figure 1b) fell rapidly. Erythrocyte counts (Figure 1c) also fell rapidly, indicating that decreased hematocrit is due to decreased erythrocytosis. For the 11 subjects with adequate follow-up, the mean rate of absolute hematocrit decrease was 1.76% per week (median: 1.81%/week; min - max: 0.65 - 2.69%) and the mean time to reach goal hematocrit below 45% was 4.79 weeks (median: 4.14 weeks, min - max: 3.57 - 8.14).Eight subjects reported adverse events (AEs). Injection site reactions (ISRs) occurred in 7 subjects and were mild or moderate in severity. The most common ISRs were erythema (n=7), induration (n=5) and pruritis (n=2). Adverse events other than ISRs that occurred in 2 or more subjects were hypertension (n=2), pyrexia (n=2) and thrombocytosis (n=2). There were two serious adverse events (worsening migraine and pleuritic chest pain) and both were considered unrelated to rusfertide. Overall, rusfertide was well tolerated.Conclusions. This study demonstrates that induction therapy with twice weekly rusfertide administration was effective in rapidly achieving target hematocrit below 45% without phlebotomy in all PV patients which was then successfully maintained with weekly rusfertide treatment. Moreover, the twice weekly injections of rusfertide used to rapidly lower hematocrit levels were safe and well tolerated.Key words: Hepcidin, Hematocrit, Rusfertide, PTG-300, Polycythemia Vera, PV, Therapeutic Phlebotomy [Display omitted] DisclosuresGupta: Protagonist Therapeutics: Current Employment. Valone: Protagonist Therapeutics: Consultancy, Current equity holder in publicly-traded company. Khanna: Protagonist: Current Employment, Current equity holder in publicly-traded company. Modi: Protagonist Therapeutics: Current Employment. Hoffman: Kartos Therapeutics, Inc.: Research Funding; Protagonist Therapeutics, Inc.: Consultancy; Novartis: Other: Data Safety Monitoring Board, Research Funding; AbbVie Inc.: Other: Data Safety Monitoring Board, Research Funding.

Outcomes with Interferon in Polycythemia Vera: A Systematic Review and Meta-Analysis

▪IntroductionPolycythemia Vera (PV) is a chronic myeloproliferative neoplasm that presents with increase proliferation of red cells as well as variable presence of thrombocytosis & leukocytosis. Currently treatment options for PV are phlebotomy, low-dose aspirin or cytoreductive therapy. Interferon (IFN) is a biological response modifier that exerts myelosuppressive action on excessively proliferative cell lineages and is also a non-leukemogenic drug. We conducted a systematic review and meta-analysis on the efficacy of Interferon for the treatment of PV.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a comprehensive literature search was conducted on PubMed, Cochrane, and Clinical trials.gov using MeSH terms and keywords for “ Polycythemia Vera ” AND “ Interferons ”. A total of 577 records were discovered using database searching. All search results were imported into the Endnote X9.0 reference manager, and duplicates were removed. After screening and excluding review and irrelevant articles, 22 original articles reporting IFN as treatment for PV in adult patients were included. The data were collected for baseline characteristics of the participants and efficacy and safety of the intervention. Quality evaluation was done using the NIH quality assessment tool. The inter-study variance was calculated using the Der Simonian-Laird Estimator. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the ‘meta’ package by Schwarzer et al. in the R programming language (version 4.16-2).ResultsA total of 1123 patients were evaluated from 22 studies. The median age was 54.5 (47.5-67) years and median follow-up time was 24 (9-146) months. The median prior number of phlebotomies was 4.55 (2-18). The type of IFN used were recombinant IFN-alpha-2a in 2 studies, IFN-a2b in 5 studies, recombinant IFN-a in 6 studies, and Pegylated-recombinant IFN-α2a in 7 studies. The pooled overall hematological response (OHR) was 86% (95% Cl 0.76-0.93, I 2= 84%, p=<0.01, n=460) with pooled complete hematological response (CHR) of 63% (95% Cl 0.50-0.76, I 2=85%, p=<0.01, n=409) and pooled partial hematological response (PHR) of 22% (95% Cl 0.12-0.34, I 2=81%, p=<0.01, n=361). Pooled overall molecular response (OMR) was 64% (95% Cl 0.56-0.71, I 2=0%, p=0.6, n=190) with pooled complete molecular response (CMR) of 24% (95% Cl 0.14-0.35, I 2=75%, p=<0.01, n=276) and pooled partial molecular response (PMR) of 38% (95% Cl 0.31-0.45, I 2=0%, p=0.5, n=191). Side effects reported were nausea, allergic reactions, liver dysfunction, dose dependent mild myalgia, fever, malaise, itching, persistent fever, headache, and flu like symptoms [Table 1].ConclusionInterferon shows promising results when used for the treatment of polycythemia vera with a durable hematologic and molecular response and has an acceptable side effects profile. However, large randomized clinical trials are needed to confirm these findings and to explore the dose and combination of interferon with other drugs.. [Display omitted] DisclosuresAbhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. McGuirk: Bellicum Pharmaceuticals: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Pluristem Therapeutics: Research Funding; Novartis: Research Funding; Allovir: Consultancy, Honoraria, Research Funding; EcoR1 Capital: Consultancy; Novartis: Research Funding; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Fresenius Biotech: Research Funding; Kite/ Gilead: Consultancy, Honoraria, Other: travel accommodations, expense, Kite a Gilead company, Research Funding, Speakers Bureau; Astelllas Pharma: Research Funding; Gamida Cell: Research Funding. Yacoub: Dynavex: Current equity holder in publicly-traded company; Cara: Current equity holder in publicly-traded company; Ardelyx: Current equity holder in publicly-traded company; Agios: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ACCELERON PHARMA: Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Hylapharm: Current equity holder in publicly-traded company.

Normal Life Expectancy for Polycythemia Vera Patients Is Possible

▪Introduction: Polycythemia vera (PV), a chronic myeloproliferative neoplasm, is characterized by shortened overall survival (OS) due to potentially fatal thrombosis, progression to myelofibrosis (MF), and acute leukemia. Treatment with aspirin, attentive phlebotomy (PHL) and cytoreductive agents can prevent thrombosis; but it is unknown whether available treatments can achieve a normal life-span for PV patients (pts). Our objective was to assess the extent by which PV alters OS of pts receiving available treatment at our center and in the community.Methods: We obtained demographics and survival data of adult PV pts from our Weill Cornell Medicine (WCM) Research Database Repository (PV-WCM) diagnosed from 1974-2020 as previously described (Abu-Zeinah et al. Leukemia 2021); and from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, 2001-2017. PV-WCM thrombosis and MF progression data were available. WCM institutional review board approval and SEER data use agreement were in place. OS of PV pts was estimated using Kaplan-Meier (KM) analysis. Propensity Score Matching was used to identify a subgroup of SEER pts (PV-SEER) with similar age, sex, and race demographics to PV-WCM for comparison of OS. Cox proportional hazards was used for multivariable analysis (MVA) of survival. Actuarial survival of the US population matched by age, sex, race, and year-of-birth was obtained from US Census. Observed OS was compared to actuarial OS using one-sided log-rank test.Results: We identified 470 PV-WCM and 16,492 PV pts from SEER. The median OS of the PV-WCM cohort and the SEER population was 26.6 and 12.8 years, respectively, but the groups differed by age and sex (Fig 1A). PV-WCM and matched PV-SEER, however, were well balanced by age, sex, and race (standardized mean difference <0.1). The median OS of PV-WCM was 10.8 years longer than PV-SEER (p<0.001, Fig 1B). MVA confirmed 65% lower mortality in the PV-WCM group relative to the PV-SEER population (p<0.001, Fig 1C). PV-SEER OS was shorter than actuarial OS of the US population (mortality HR 2.47, p<0.001), whereas PV-WCM OS was not significantly different than expected (mortality HR 1.15, p=0.136). Excess late mortality was observed in PV-WCM after 17 years, potentially due to increased incidence of MF progression, affecting almost 50% of PV pts after 25 years (Fig 1D).Discussion: These data point to the success of attentive management with aspirin, targeted PHL, and cytoreductive therapy at a specialty center in reducing the mortality of PV, owing in part, to ELN and NCCN treatment recommendations for preventing fatal thrombosis. Although excess thrombosis was not eliminated in PV-WCM pts, the incidence rate was low after the first two years (Fig 1D). In contrast, the incidence of MF progression increased, potentially contributing to excess late mortality. Current PV risk stratification and treatment recommendations neither predict nor aim to mitigate progression to MF, and do not satisfy the needs of younger, low-risk pts who are often symptomatic and harbor a lifetime threat of progression (Fig 1E). The recent Low-PV study showed that low-risk pts may also benefit from cytoreductive therapy with an agent such as interferon-alpha (rIFNα) over PHL alone (Barbui et al. Lancet Hematol 2021). PV-WCM pts treated with rIFNα (n=137), previously shown to have improved MF-free survival and OS (Abu-Zeinah et al. Leukemia 2021), had an OS similar to the matched US population (p=0.33, Fig 1F); whereas pts not treated with rIFNα had modestly shortened OS (HR 1.26, p=0.03). Because PV progression is among the leading causes of late morbidity and mortality, and available therapy can mitigate this, it may be time to reconsider and improve upon PV risk stratification and treatment.Conclusion: This large population-based and single center study shows that although PV survival remains shortened, normal life expectancy for PV pts is possible with available care. The discrepancy between survival in the community and at a specialized center highlights the need for greater community outreach, health equity, and education regarding treatment standards for PV. Hopefully, this study motivates development of new PV risk stratification and treatment recommendations that focus not only on hematologic control and thrombosis prevention, but also on preventing MF progression, improving OS, and restoring normal life expectancy. [Display omitted] DisclosuresAbu-Zeinah: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Silver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees ; MPN-RF (Foundation): Research Funding; Constellation: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure:Interferon-alpha is used off label in the treatment of polycythemia vera.

Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for Hospitalised Patients with Mild or Moderate COVID-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomised Controlled Trial

Multi-Arm Trial of Inflammatory Signal Inhibitors (MATIS) for Hospitalised Patients with Mild or Moderate COVID-19 Pneumonia: A Structured Summary of a Study Protocol for a Randomised Controlled Trial

Ropeginterferon alfa-2b in patients with genotype 1 chronic hepatitis C: Pharmacokinetics, safety, and preliminary efficacy.

ABSTRACTBackground and AimRopeginterferon alfa‐2b (P1101) is a novel long‐acting mono‐PEGylated recombinant proline interferon (IFN) conjugated to a 40 kDa branched polyethylene glycol (PEG) chain at its N‐terminus, allowing every‐two‐week injection. It received European Medicines Agency and Taiwan marketing authorization for the treatment of polycythemia vera in 2019 and 2020, respectively. This phase 2 study aimed to evaluate the pharmacokinetics, safety, and preliminary efficacy of ropeginterferon alfa‐2b as compared with PEG‐IFN‐α2a in patients with chronic hepatitis C virus genotype 1 infection.MethodsOne hundred six treatment naive patients were enrolled in this phase 2 study and randomized to four treatment groups: subcutaneous weekly PEG‐IFN‐α2a 180 μg (group 1), weekly ropeginterferon alfa‐2b 180 μg (group 2), weekly ropeginterferon alfa‐2b 270 μg (group 3), or biweekly ropeginterferon alfa‐2b 450 μg (group 4) plus ribavirin for 48 weeks.ResultsAfter multiple weekly administration, serum exposure (AUC0‐τ) in ropeginterferon alfa‐2b 180 μg was approximately 41% greater and the accumulation ratio of 2‐fold greater than PEG‐IFN‐α2a 180 μg. The incidences of flu‐like symptoms were 66.7% (18/27), 53.3% (16/30), 55.0% (11/20), and 48.3% (14/29), anxiety were 14.8% (4/27), 6.7% (2/30), 0%, and 0%, and depression were 25.9% (7/27), 13.3% (4/30), 0%, and 3.4% (1/29), for groups 1–4, respectively. Two grade 2 of 3 depression were noted in PEG‐IFN‐α2a arm, but none in ropeginterferon arms. The SVR24 rates were 77.8% (21/27), 66.7% (20/30), 80% (16/20), and 69% (20/29), respectively.ConclusionsRopeginterferon alfa‐2b showed longer effective half‐life and superior safety profile than PEG‐IFN‐α2a. Biweekly injection of ropeginterferon alfa‐2b will be studied in larger viral hepatitis patient population.

Targeting Cell Non-Autonomous MAPK Activation As a Novel Therapeutic Strategy in Myeloproliferative Neoplasms

Activated JAK2 signaling is a central feature of myeloproliferative neoplasm (MPN) pathogenesis, and drives myeloid blood cell production through constitutive activation of STAT transcription factors, the PI3K/AKT and the MAPK signaling pathways. JAK2 inhibitors show significant, but limited clinical efficacy such as seen for ruxolitinib, a type I JAK1/2 inhibitor approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). Given the impact of JAK2 inhibition on the MAPK signaling pathway in MPN has not been studied in vivo, we hypothesized that MAPK signaling could contribute to MPN cell survival in the setting of JAK kinase inhibition.We observed that JAK2 inhibition by ruxolitinib and other agents suppressed phosphorylation of ERK1/2, the distal kinases in the MAPK pathway, in MPN cell lines. By contrast, these JAK2 inhibitors could not suppress MAPK signaling in vivo in Jak2 V617F- and MPL W515L-driven murine MPN models. In the in vivo setting, ERK remained fully activated despite JAK2 inhibition at therapeutic or higher doses suggesting that compensatory signaling may bypass JAK2 inhibition. E x vivo exposure of Jak2 V617F and MPL W515L primary mouse hematopoietic cells or PBMCs from JAK2 V617F mutant MPN patients to ruxolitinib demonstrated MAPK inhibition, indicating that cell extrinsic stimuli maintain ERK activation in vivo .To identify secreted factors which could mediate JAK-independent ERK activation in vivo, we performed receptor tyrosine kinase arrays in Jak2 V617F and MPL W515L mouse splenocytes in presence and absence of ruxolitinib. This allowed us to show that expression and activation of PDGFRα was maintained in MPN cells upon JAK inhibitor treatment. Although the production of multiple cytokines was reduced by ruxolitinib, PDGFA and PDGFB production were not attenuated by JAK2 inhibitor treatment. We confirmed that PDGF-BB was present at higher levels than PDGF-AA in bone marrow supernatant, spleen supernatant and serum suggesting it is the primary ligand activating MAPK signaling through PDGFRα. Stimulation of primary Jak2 V617F bone marrow and spleen cells with PDGF-BB ex vivo induced ERK activation in presence of ruxolitinib suggesting PDGF-BB can mediate bypass ERK activation.We next assessed the efficacy of combined JAK/MEK inhibition in vivo . Binimetinib, a clinical-grade MEK1/2 inhibitor, inhibited ERK phosphorylation in Jak2 V617F and MPL W515L murine models at a single dose or with extended treatment, and showed modest efficacy when given as monotherapy in vivo. Of note, dual targeting of JAK2 and MEK with combined ruxolitinib/binimetinib was superior to both single agent therapies. In the Jak2 V617F model of PV, dual JAK/MEK inhibition corrected splenomegaly and reduced the increased hematocrit, reticulocytes, erythroid and megakaryocytic-erythroid progenitor populations characteristic of this MPN model. Bone marrow and spleen fibrosis was resolved by dual JAK/MEK inhibition along with reduced bone marrow hypercellularity and decreased mutant allele burden. Expression of ERK downstream targets including ETV5, EGR1, CCND1, DUSP4, DUSP6 and SPRED2 was effectively reduced by combined JAK/MEK inhibitor therapy. Dual JAK/MEK inhibition with ruxolitinib/binimetinib also showed increased efficacy in the MPL W515L model of ET/MF with improved correction of leuko- and thrombocytosis, extramedullary hematopoiesis, hepato- and splenomegaly and megakaryocytic hyperplasia. Combined JAK/MEK inhibition with ruxolitinib/selumetinib showed similar effects. Importantly, dual JAK/MEK inhibition reversed fibrosis to an extent not seen with JAK inhibitor monotherapy.Taken together, these data demonstrate that JAK2 inhibition incompletely suppresses ERK activation in MPN in vivo and that cell non-autonomous ERK activation through PDGFRα contributes to the limited efficacy of JAK inhibition in MPN. We show that dual targeting of JAK2 and MEK provides improved therapeutic efficacy by preventing bypass ERK activation and suggest that dual JAK/MEK inhibition should be pursued as a therapeutic approach for MPN patients. Our data also suggest that cell non-autonomous MAPK activation might represent a mechanism of resistance to targeted therapies which is only observed in the in vivo setting and which can guide combination therapy trials in different malignant contexts. [Display omitted] DisclosuresRadimerski:Novartis: Employment. Skoda:Novartis: Consultancy, Speakers Bureau; Shire: Speakers Bureau; Baxalta: Consultancy, Speakers Bureau. Levine:Roche: Research Funding; Celgene: Research Funding; Celgene: Research Funding; Roche: Research Funding; Qiagen: Equity Ownership; Qiagen: Equity Ownership.

Ruxolitinib Inhibits Toll-like Receptor or GM-CSF, but Not TREM-1 Mediated Neutrophil Activation

Introduction: Ruxolitinib (RUX) is the first Janus kinase (JAK)1/2 inhibitor approved for the treatment of myelofibrosis (MF) or polycytemia vera (PV), as the pathogenesis of these myeloproliferative neoplasms is linked to a dysregulation of JAK signaling. In clinical trials, RUX demonstrates a profound reduction of splenomegaly and constitutive symptoms along with an improved quality of life. The most frequent adverse events of RUX include anemia and thrombocytopenia. However, beyond this, severe infectious complications have been reported in association with RUX treatment, such as C. neoformans pneumonia, toxoplasmosis retinitis and hepatitis B virus reactivation, indicating immunosuppressive effects of this drug. On the cellular level, RUX has yet been characterized as a negative regulator for NK- and T-cell functions, possibly accounting for the side effects observed. In our present work, we focused on the impact of RUX on polymorphonuclear neutrophil (PMN) activation as important regulators of the innate immune response.Methods: Purified PMN from healthy human donors were isolated by dextran sedimentation and HistopaqueÒ centrifugation and pretreated with RUX. PMN were activated with anti-TREM-1 agonistic antibody (6B1), isotope matched control antibody (4C9) (both own production), lipopolysaccharide (LPS), zymosan or GM-CSF and effector functions like phagocytosis by fluorochrome labeled polystyrene beads, L-selectin (CD62L) shedding, oxidative burst and IL-8 secretion were analyzed. In addition, blood samples of patients under RUX treatment and samples of age matched healthy volunteers were stimulated either with GM-CSF, LPS or zymosan. Afterwards functionality of PMN was analyzed by determination of oxidative burst, phagocytosis, L-selectin shedding and degranulation.Results: Ligation of TREM-1 (by specific antibody), TLR2/6 (by zymosan), TLR4 (by LPS) or GM-CSF-R induced a strong activation of PMN derived from healthy human donors, as shown by initiation of oxidative burst, increased phagocytic activity as well as CD62L shedding and release of IL-8. The additional presence of RUX revealed an impaired phagocytosis, CD62L shedding and IL-8 production after activation with the TLR agonists (LPS, zymosan) or GM-CSF, whereas no profound impact of pretreatment was observed on TREM-1 mediated effector functions. These results suggest that the inhibition of JAK signaling affects TLR and GM-CSF mediated PMN activation, while this particular pathway appears functionally irrelevant for TREM-1 mediated PMN activation. In line with these results, we observed impaired PMN functions in patients receiving RUX treatment compared to healthy controls with the most impressive impact on the oxidative burst and phagocytosis after LPS or zymosan stimulation.Conclusion: These data provide deeper insights on the impact of RUX as an immunosuppressant of innate immunity on the cellular level adding the selective inhibition of distinct PMN activating receptor pathways. The observation of impaired effector functions of PMN after RUX pretreatment in vitro as well as in vivo may help to explain the severe infectious complications accompanying MF or PV. DisclosuresKindler:Novartis: Membership on an entity's Board of Directors or advisory committees. Radsak:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Gilead: Other: Travel support; Acceleron: Research Funding.

Ruxolitinib in Refractory Acute and Chronic Graft-Versus-Host Disease: A Multi-Center Survey Study

1. INTRODUCTIONGraft-versus-host disease (GVHD) is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). First-line treatment is based on the use of high doses of corticosteroids. However, more than 50 % of patients will develop treatment failure with no treatment strategies approved for subsequent lines. Ruxolitinib is an orally administered selective Janus Kinase (JAK) inhibitor approved for the treatment of myelofibrosis and polycythemia vera. It has been previously reported its effectiveness in the treatment of GVHD in pre-clinic models and results in the clinical setting have recently been reported.2. METHODSBetween October 2015 to July 2017, 79 patients received ruxolitinib under a compassionate use program and were evaluated in this retrospective study using data collected from 13 Spanish centers. The median age was 51 years (range, 0-73). The most frequent underlying diseases were: acute myeloid leukemia (38 %), non-Hodgkin lymphoma (16.5 %) and acute lymphoblastic leukemia (15.2 %). The majority of patients received reduced-intensity conditioning regimens (57 %). Patient baseline characteristics of the entire population are shown in table 1. Patients were scored for their best response at any time after starting ruxolitinib. Treatment responses were considered when patients achieved CR or PR.3. RESULTSTwenty-two patients received ruxolitinib for refractory acute GVHD (aGVHD). All patients had grades 2-4 aGVHD and 19 patients (86.5%) had grades 3-4; the median number of previous lines of therapy was 2 (range 1-5). Overall response rate was 68.2% (15/22) which was obtained after a median of 2 weeks of treatment, and 18.2% (4/22) reached CR. We found no differences in treatment responses when analyzed by type of organs involved (table 2). The use of ruxolitinib allowed to taper steroids doses in 16/22 of patients (72%). Cytomegalovirus (CMV) reactivation was observed in 12/22 patients (54.5%). After one year, overall survival was 0.43 (IC: 0.2-0.66).Fifty-seven patients were evaluated for refractory chronic GVHD (cGVHD). All patients had moderate (32/57, 56.1 %) to severe (25/57, 43.9%) cGVHD. The median number of previous lines of therapy was 3 (range 1-10). Overall response rate was 57.9% (33/57) with 5.3 % (3/57) obtaining CR, with no differences found when analyzed by type of organs involed. Thirty-three patients (57%) could diminished steroids doses a. Cytomegalovirus (CMV) reactivation was observed in 11/57 patients (19.3 %). After one year, overall survival was 0.81 (IC: 0.7 -0.92).Median dose was 20 mg/day. Overall, 26 patients (32.9 %) discontinued ruxolitinib due to: lack of response (14), cytopenias (3 patients had thrombocytopenia, 3 anemia, 3 had both); infections (1); other causes (2). Only three patients discontinued ruxolitinib due to drug-related toxicities (table 3).Globally, 18 patients (22.8 %) died: 10/22 patients (45.5%) within the aGVHD and 8/57 patients (14 %) within the cGVHD subgroup. Causes of death were: infections (10), refractory GVHD (6) and other causes (4). Relapse occurred in 1 non ruxolitinib-responsive patient.4. DISCUSSIONRuxolinitinb in real life setting has been shown as a effective and safety treatment option for GVHD patients, with ORR of 68.3% and 57.9% for refractory aGVHD and cGVHD respectively in heavily pretreated patients (1-10 previous lines). Ruxolitinib may be an alternative option to consider for steroid-refractory acute and chronic GVHD patients beyond first line treatment. [Display omitted] DisclosuresGarcía Gutiérrez:Incyte: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

Advances in the Treatment of Polycythemia Vera: Trends in Disease Management.

Treatment modalities for polycythemia vera (PV) have evolved over time. Phlebotomy and low-dose aspirin suffice in low-risk patients, but cytoreductive therapies are indicated in all high-risk patients (age ≥ 65 years or those with a history of PV-related thrombotic event) and may be considered for low-risk patients with progressively increasing splenomegaly, progressively increasing leucocyte and platelet counts, and for those who do not tolerate phlebotomy. Hydroxyurea/hydroxycarbamide or interferons can be used as first-line drugs. Hydroxyurea may not be tolerated by some patients, and it also carries risk of myelosuppression. Interferon alfa is especially useful for PV symptoms, and the newer preparation, ropeginterferon alfa-2b, has lesser incidence of flu-like reactions. Ruxolitinib reduces the JAK2V617F mutation burden and is used as a second-line drug. Anagrelide reduces platelet production and can be used in conjunction with hydroxyurea in patients with excessive thrombocytosis. The alkylating agent, busulfan, can also be used as a last resort in patients with a limited life expectancy. Prospective future treatments include givinostat, a histone deacetylase inhibitor, and idasanutlin, a murine double minute 2 antagonist.

Recent advances in prognostication and treatment of polycythemia vera.

Polycythemia vera (PV) is a BCR-ABL–negative myeloproliferative neoplasm marked by acquisition of an activating mutation of JAK2, which leads to not only erythrocytosis but also frequently to leukocytosis and thrombocytosis, and is associated with a high symptom burden and increased thrombotic risk. PV has the potential to progress to myelofibrosis or an aggressive form of acute myeloid leukemia. Mutational profiling of patients with PV has led to the development of risk stratification tools to determine an individual’s risk of developing progressive disease. Although the current goals of PV treatment are to alleviate symptoms and reduce thrombotic risk, there are growing efforts to identify disease-modifying agents which will also prevent progression of disease. Here, we give an overview of the developing prognostic tools and therapeutic landscape for PV, focusing on four drug classes: pegylated interferon-alpha 2, MDM2 antagonists, hepcidin mimetics, and histone deacetylase inhibitors.

Prophylactic Ruxolitinib for Cytokine Release Syndrome (CRS) in Relapse/Refractory (R/R) AML Patients Treated with Flotetuzumab

Introduction: CRS is a potentially life-threatening toxicity observed following T cell-redirecting therapies. CRS is associated with elevated cytokines, including IL6, IFNγ, TNFα, IL2 and GM-CSF. Glucocorticosteroids (GC) and the IL6 receptor blocking antibody tocilizumab (TCZ) can reduce CRS severity; however, CRS may still occur and limit the therapeutic window of novel immunotherapeutic agents. Disruption of cytokine signaling via Janus kinase (JAK) pathway interference may represent a complementary approach to blocking CRS. Ruxolitinib (RUX), an oral JAK1/2 inhibitor approved for the treatment of myelofibrosis and polycythemia vera, interferes with signaling of several cytokines, including IFNγ and IL6, via blockade of the JAK/STAT pathway. We hypothesized that RUX may reduce the frequency and severity of CRS in R/R AML patients (pts) undergoing treatment with flotetuzumab (FLZ), an investigational CD123 x CD3 bispecific DART® molecule. Methods: Relapse/refractory (including primary induction failure, early relapse and late relapse) AML pts were included in this study. RUX pts were treated at a single site, Washington University, St. Louis, MO. RUX was dosed at 10 mg or 20mg BID days -1 through 14. Comparator (non-RUX) pts (n=23) were treated at other clinical sites. FLZ was administered at 500 ng/kg/day continuously in 28-day cycles following multi-step lead-in dosing in week 1 of cycle 1. CRS was graded per Lee criteria1. Results: As of July 1st, 2020, 10 R/R AML pts, median age 65 (range 40-82) years, have been enrolled and treated in the RUX cohort (6 at 10mg, 4 at 20 mg of RUX). All pts had non-favorable risk by ELN 2017 criteria (8 adverse and 2 intermediate); 1 (10.0%) pt had secondary AML; pt characteristics in the RUX and non-RUX cohorts were balanced, except for median baseline BM blasts which was higher in non-RUX pts: 15% (range 5-72) vs (40% (range 7-84), RUX and non-RUX pts respectively. Cytokine analysis showed statistically significant (p&amp;lt;0.05) lower levels of IL4, IL12p70, IL13, IL15, IL17A, IFNα2, but higher levels of GM-CSF were measured in RUX vs non-RUX pts, specifically during co-administration with FLZ (Fig. 1). However, incidence and severity of CRS events were similar. In the RUX cohort, 9 (90%) pts experienced mild to moderate (grade ≤ 2; 48.6% of events were grade 1) CRS events whereas no grade ≥ 3 CRS were reported; in the non-RUX cohort, 23 (100%) pts experienced mild to moderate (grade ≤ 2; 73.1% of events were grade 1) CRS events, 1 (4.3%) grade ≥ 3 CRS was reported. Most CRS events occurred in the first 2 weeks of FLZ administration (75% and 92%, respectively). No differences in duration of CRS events were noted. However, more CRS-directed treatment was used in the RUX cohort. Five (50%) pts received a total of 12 doses of TCZ, 1 (10%) pt received GC and 1 (10%) pts received vasopressors in the RUX cohort. In the non-RUX cohort, 5 (21.7%) pts received 8 doses of TCZ, 3 (13.0%) pts received GC and 1 (3.7%) pt received vasopressors. Dose intensity (DI) at FLZ dose of 500 ng/kg/day was comparable, with median DI of 97.6% and 98.0% in RUX and non-RUX cohorts, respectively. Time to first response (TTFR; BM &amp;lt; 5% blasts) and time on treatment (ToT) were similar between both groups. Median TTFR was 1 cycle for both groups (range 1-2 cycles), and median ToT was 1.4 (range 0.9-5.1) and 1.8 (range 1.3-5.1) months, for RUX and non-RUX pts, respectively. Complete response rate (BM &amp;lt; 5% blasts) was similar: 4 (40%) in RUX pts, and 8 (34.8%) in non-RUX pts; 2 RUX (50%) and 5 non-RUX (62.5%) responders transitioned to stem cell transplant. Conclusion: Prophylactic RUX produced a clear difference in cytokine profiles but no discernable improvement in clinical CRS or response rates in FLZ treated patients. A larger study may be required to determine the prophylactic role of RUX in CRS.

Ropeginterferon Demonstrates Safety and Efficacy in Myelofibrosis: Pilot Study Results

Background: Myelofibrosis (MF) is a clonal bone marrow disorder characterized by a constitutional symptoms, splenomegaly, anemia, elevated WBC and bone marrow fibrosis. Ruxolitinib is a JAK2 inhibitor approved for patients with Intermediate-2 (INT-2) or high risk disease based on dynamic international prognostic scoring system (DIPSS), however, there are limited options for patients with early disease. Interferon alpha (IFNa) is a cytokine therapy that has been used in treatment of chronic myelogenous leukemia and polycythemia vera (PV). In these diseases, there can be a reduction in the clonal burden in addition to a hematologic response. Therefore, we sought to use this therapy in patients with MF. Methods: Patients who had MF were enrolled on an IRB approved clinical protocol in a single arm, single institution study. Patients were stratified to either an early disease arm (characterized by intermediate 1 (INT-1) risk or advanced disease (Int-2 or high-risk disease based on DIPSS). Patients were started on ropeginterferon (interferon-alpha 2b) at 50 ug every two weeks, and the dose was titrated up to either 300 ug every other week, or until unacceptable toxicity. Patients were monitored for response based on IWG criteria. Results: Ten patients with MF have been enrolled on the study to date (Early: 3, Int/High: 7). Median age was 69.5 (39 - 88), four patients were female. Five patients had primary MF (PMF), 4 had post-essential thrombocythemia and 1 post PV MF. Five patients had previous treatment for their disease. Four patients continue to receive active treatment (2 early disease, and 2 advanced disease). Reasons for stopping include disease progression (3), toxicity (1), alternate treatment (1) and lack of benefit (1). The median number of cycles for those who ended treatment was 7.5 (4-47), and for those who remain on treatment, they range from 16 - 46 cycles. Five patients achieved a clinical improvement, 3 had a spleen response, and 2 had a symptom response. A grade 3 adverse event (AE) potentially attributable to the treatment occurred in 6 patients (60%), 4 (40.0%) patients had anemia, and 2 (20.0%) patients had lymphopenia. Only one patient discontinued therapy due to AEs (dizziness, atrial fibrillation). One death has occurred to date, due to an unrelated cause. Discussion: Ropeginterferon is a well-tolerated therapy that results in clinical improvement in half the patients, and appears to be well tolerated. These results, along with historic data suggesting possible reduction in clonal burden, suggest that ongoing studies are warranted to further understand the clinical benefit of ropeginterferon. Disclosures Zimmerman: Pharmaessentia: Current Employment. Mesa:Incyte: Research Funding; AbbVie: Research Funding; Sierra Oncology: Consultancy; CTI BioPharma: Research Funding; Promedior: Research Funding; Genentech: Research Funding; Novartis: Consultancy; Samus Therapeutics: Research Funding; LaJolla Pharmaceutical Company: Consultancy; Bristol Myers Squibb: Research Funding. OffLabel Disclosure: Clinical trial

A pharmacokinetic evaluation of ropeginterferon alfa-2b in the treatment of polycythemia vera

ABSTRACT Introduction Polycythemia vera (PV) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm (MPN). A newly developed PV treatment option, ropeginterferon alfa-2b, contains recombinant human alfa monoisomer as an active ingredient, resulting in a novel pharmacologic profile and improved tolerability. Efficacy studies conclude remarkable long-term hematological response and sustained JAK2V617F allele burden reduction. Ropeginterferon alfa-2b compound has been approved for the treatment of polycythemia vera without symptomatic splenomegaly. Areas covered Current clinical trials are investigating the role of ropeginterferon alfa-2b in the first-line setting of treatment for PV. The safety and efficacy results of completed trials are summarized in this review. Metabolic, pharmacokinetic issues are also discussed of ropeginterferon alfa-2b. Expert opinion Ropeginterferon alfa-2b is a targeted therapeutic option in the treatment of PV, representing a significant improvement compared to conventional cytoreductive therapies. The single isomer entity of the recombinant human interferon alfa-2b and the mono-pegylation method imparts favorable properties to the compound. The use of ropeginterferon alfa-2b allows extended dosing interval, reduces side effects, and may increase the overall survival of PV patients by reducing the risk of progression to myelofibrosis or acute leukemia. Clinical data suggests that the compound may provide a disease-modifying option for PV patients with asymptomatic splenomegaly.