Peginterferon Alfa-2b Research Articles

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon

BackgroundHBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AimTo evaluate the use of serum biomarkers to predict HBeAg loss. MethodsHBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. ResultsHBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03–0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67–374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18–0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. ConclusionsBaseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

A high functional cure rate was induced by pegylated interferon alpha-2b treatment in postpartum hepatitis B e antigen-negative women with chronic hepatitis B virus infection: an exploratory study.

Limited data have been reported on achieving functional cure using pegylated interferon (Peg-IFN) alpha-2b treatment for postpartum hepatitis B e antigen (HBeAg)-negative women with chronic hepatitis B virus (HBV) infection. This study was to assess the effectiveness and safety of Peg-IFN alpha-2b in HBV postpartum women without HBeAg and identify factors linked to the functional cure. A total of 150 HBeAg-negative postpartum women were retrospectively recruited.47 patients received Peg-IFN alpha-2b [Peg-IFN(+) group] and 103 patients did not [Peg-IFN(-) group]. Propensity score matching (PSM) was used to adjust the baseline imbalance between the two groups. The patients were followed for at least 48 weeks. The primary endpoints were hepatitis B surface antigen(HBsAg) loss and HBsAg seroconversion at 48 weeks. Logistic regression analysis was used to assess factors associated with HBsAg loss at 48 weeks. At week 48,the HBsAg loss and seroconversion rate in Peg-IFN(+) group were 51.06%(24/47) and 40.43%(19/47), respectively. Even after PSM, Peg-IFN(+) group still showed higher HBsAg loss rate (50.00% vs 7.14%,p<0.001) and higher HBsAg seroconversion rate (38.10% vs 2.38%,p<0.001). Baseline HBsAg levels (Odds Ratio [OR]: 0.051, 95% Confidence Interval [CI]: 0.003-0.273, P=0.010), HBsAg at week 24 (OR:0.214, 95%CI:0.033-0.616, P=0.022), HBsAg decline at week 24 (OR:4.682, 95%CI: 1.624-30.198, P=0.022) and postpartum flare (OR:21.181, 95%CI:1.872-633.801, P=0.030) were significantly associated with HBsAg loss at week 48 after Peg-IFN alpha-2b therapy. Furthermore, the receiver operating characteristic curve (ROC) showed that the use of baseline HBsAg<182 IU/mL, HBsAg at week24 < 4 IU/mL and HBsAg decline at week24>12IU/mL were good predictors of HBsAg loss. No serious adverse events were reported. Peg-IFN alpha-2b treatment could achieve a high rate of HBsAg loss and seroconversion in HBeAg-negative postpartum women with reliable safety, particularly for patients experience postpartum flare and have low baseline HBsAg levels.

Efficacy and safety of pegylated interferon alpha-2b for patients with myeloproliferative neoplasm

Objective: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) in the treatment of myeloproliferative neoplasm (MPN). Methods: Thirty-four MPN patients receiving PEG-IFN-α2b treatment in the Second Hospital of Tianjin Medical University from August 2019 to October 2022 were prospectively included. Among the patients, 9 were male and 25 were female, and the median age [M (Q1, Q3)] was 57 (19, 78) years. Patients' clinical characteristics were collected and the follow-up was performed. As of January 30, 2023, the follow-up period [M(Q1, Q3)] was 24 (16, 33) months. The efficacy, safety and changes in immune cell and cytokine levels after 12 and 24 months of treatment were analyzed. Results: During the follow-up period, 4 patients dropped out, and the efficacy was evaluable in 30 patients. Following 12 and 24 months of treatment, the complete hematologic response (CHR) rates were 57.1% (16/28) and 75.0% (18/24), respectively. The complete molecular response (CMR)+partial molecular response (PMR) rates were 27.3% (6/22) and 55.0% (11/20), respectively. The bone marrow histopathological overall response rates (ORR) were 34.6% (9/26) and 47.6% (10/21), respectively. At 12 and 24 months of treatment, the proportions of CD8+HLA-DR+T cells, effector T cell subpopulations, CD56bright natural killer (NK) cells, and plasmacytoid dendritic cells (pDC) were higher than the pre-treatment levels, while the proportion of CD56dim NK cells was lower than the pre-treatment level (all P<0.05). The levels of motif chemokine ligand 10 (CXCL10), tumor necrosis factor (TNF)-α and TNF-β in bone marrow all increased from those prior to treatment, while the levels of vascular endothelial growth factor (VEGF) and interleukin (IL-4) decreased from those prior to treatment (all P<0.05). Among hematological adverse reactions, white blood cells decrease [47% (16/34)] was observed with high incidence. Among non-hematological adverse reactions, asthenia [44.1% (15/34)] and transaminases increase [32.3% (11/34)] were observed with high incidences. Conclusions: PEG-IFN-α2b has high hematologic, molecular, and bone marrow histopathological response rates in the treatment of MPN. It can reduce malignant clone loads and regulate the immune microenvironment and is safe and well tolerated overall.

A simple-to-use score system for predicting HBsAg clearance to peginterferon alfa-2b in nucleoside analogs-experienced chronic hepatitis B patients

ObjectivePatients with chronic hepatitis B (CHB) often fail to achieve clearance of the hepatitis B surface antigen (HBsAg) with peginterferon treatment. Our study aimed to develop a simple-to-use scoring system to predict the likelihood of HBsAg clearance following treatment with peginterferon alfa-2b(PEG-IFN-α2b) in patients with CHB.MethodsA total of 231 patients were enrolled and divided into HBsAg clearance (n = 37) and non-HBsAg clearance (n = 194) groups. Multifactor logistic models were constructed using univariate and multiple logistic regression analyses. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis were used to evaluate the discrimination, calibration, and clinical applicability of the predictive scoring system.ResultsFour clinical variables (age, baseline HBsAg level, HBsAg level decline at week 12, and alanine aminotransferase ratio at week 12) were independently associated with HBsAg clearance after PEG-IFN-α2b treatment and, therefore, were used to develop a predictive scoring system ranging from 0 to 13. The optimal cut-off value was &amp;gt;4, with a sensitivity of 86.49%, specificity of 72.16%, positive predictive value of 37.2%, negative predictive value of 96.6%, and an AUC of 0.872. This model exhibited good discrimination, calibration, and clinical applicability. Among patients with scores &amp;lt;4, 4, or &amp;gt; 4 HBsAg clearance was achieved in 0.85, 14.29, and 37.21% of the patients, respectively.ConclusionThe scoring system could effectively predict the predominance of HBsAg clearance after PEG-IFN-α2b treatment in the early stage. This may be helpful when making clinical decisions for the treatment of patients with CHB.

Treatment Free Remission after Nilotinib Plus Peg-Interferon Alpha Induction and Peg-Interferon Alpha Maintenance Therapy for Newly Diagnosed Chronic Myeloid Leukemia Patients; The Tiger Trial

Background: The TIGER-trial (NCT01657604) is a multicenter, randomized phase III study to evaluate efficacy and tolerability of nilotinib (NIL) vs NIL+pegylated interferon alpha2b (IFN) combination therapy with IFN maintenance as first-line treatment for patients (pts) with chronic myeloid leukemia (CML) in chronic phase. Methods: A total of 717 pts were recruited from 110 sites in Germany, Switzerland, and the Czech Republic. A pilot phase (n=25) validated the feasibility of the combination of NIL 300 mg BID and IFN (30-50µg/week according to tolerability and commenced after ≥6 weeks NIL monotherapy). In the main phase, 692 pts were randomly assigned to NIL (n=353) and NIL/IFN (n=339). Achievement of major molecular remission (MMR, BCR::ABL1 ≤0.1% on the International Scale, IS) after &amp;gt;24 months (mo) of therapy was the trigger to start the maintenance phase; treatment-free remission (TFR) started in pts with ≥12 mo persistence of MR 4 ( BCR::ABL1 ≤0.01% IS) after &amp;gt;36 mo total therapy. Quality of life (QoL) was evaluated using EORTC QLQ-C30 and CML24 questionnaires. Results: From 692 randomized pts, 411 were male (59%), median age was 51 years (range, 18-85). In the monotherapy arm, median treatment duration with NIL was 3.1 years (0.02-8.9), median daily dose 600 mg (183-764). In the combination arm, median treatment duration with NIL was 2.3 years (0.02-9.1), median daily dose 600 mg (106-792). Median duration of IFN therapy was 2.4 years (0-9.0). A median of 77 (0-485) IFN injections were administered, the median dose of IFN per injection was 30µg (0-50). Probabilities of MMR and MR 4.5 ( BCR::ABL1 ≤0.0032% IS, Fig 1) by 24 mo were 89% (95% CI: 85-92%) and 49% (44-55%) vs 93% (89-95%) and 64% (59-69%) with NIL vs NIL/IFN, respectively. In 356 pts (53%) qualifying for the discontinuation phase (NIL, n=197; NIL/IFN, n=159), probabilities of maintained MMR by 24 mo were 53% (45-60%) and 62% (54-70%) after NIL and NIL/IFN, respectively, in an intention-to-treat-analysis (p=0.13). 273 (40%) eligible pts actually discontinued therapy (per-protocol-analysis, NIL, n=163; NIL/IFN, n=110). Probabilities of TFR by 24 mo were 53% (45-61%) vs 59% (49-68%) for NIL and NIL/IFN, respectively (Fig 2). Fifteen pts (2.2%) with atypical BCR::ABL1 transcripts (e1a2, n=7; e19a2, n=4; e8a2, n=2; e13a3 and e14a3, n=1 each) were randomized to receive NIL (n=7) or NIL/IFN (n=8). After a median treatment period of 37 mo (36-39) 9 pts achieved and maintained a BCR::ABL1 reduction of at least 4 orders of magnitude and were eligible for TFR. 6 pts failed to achieve an individual transcript decline by at least 3 logs. TFR was commenced in 7 and maintained in 6 pts after 32 (range, 20-84) mo. Adverse events of special interest grades 3-5 were arterio-vascular disorders in 9 vs 8%, fatigue in 2 vs 4%, thrombocytopenia in 8 vs 8%, and alanine aminotransferase elevation in 4 vs 9% of pts in the NIL vs NIL/IFN arms, respectively. QoL analyses revealed the perception of a decreased cognitive function and higher rates of fatigue in pts in the NIL/IFN arm, particularly in pts older than 40 years. In total, 24 pts (NIL, n=13; NIL/IFN, n=11) progressed to advanced disease. By 8 years, progression-free survival was 94% (95% CI: 90-96%) and 92% (88-95%), overall survival 95% (92-97%) and 94% (91-97%) in the NIL and NIL/IFN arms, respectively. 28 pts (3.9%) received an allogeneic stem cell transplantation, 14 after disease progression. 35 pts died (NIL, n=18; NIL/IFN, n=17), 9 related to CML. Conclusions: Survival of CML pts has reached probabilities close to normal. The combination of NIL with IFN is associated with a higher rate of molecular responses but also impaired tolerability. IFN maintenance is feasible, and resulted in a trend towards higher rates of long-term TFR. The study was conducted on behalf of the German CML Study Group in cooperation with the East German Study Group on Hematology and Oncology (OSHO) and the Swiss Group for Clinical Cancer Research (SAKK).

Long Term HBsAg Responses to Peg-Interferon Alpha-2b in HBeAg Negative Chronic Hepatitis B Patients Developing Clinical Relapse after Stopping Long-Term Nucleos(t)ide Analogue Therapy

Long Term HBsAg Responses to Peg-Interferon Alpha-2b in HBeAg Negative Chronic Hepatitis B Patients Developing Clinical Relapse after Stopping Long-Term Nucleos(t)ide Analogue Therapy

SAT-193 - Efficacy and prediction analysis of pegylated interferon alpha-2b in treatment-naive HBeAg negative chronic hepatitis B patients with normal ALT: a multicenter real-world study (Ice-breakting Project in China)-Interim analysis

SAT-193 - Efficacy and prediction analysis of pegylated interferon alpha-2b in treatment-naive HBeAg negative chronic hepatitis B patients with normal ALT: a multicenter real-world study (Ice-breakting Project in China)-Interim analysis

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

Interventions for dialysis patients with hepatitis C virus (HCV) infection.

Peripheral Circulating Exosomal-miRNAs Potentially Mediate the Sensitivity to Interferon Treatment in Chronic Hepatitis B Virus Patients.

Pegylated interferon alfa-2b (Peg-IFN α-2b), a first-line treatment for hepatitis B virus (HBV) infection, can significantly achieve HBsAg clearance in clinic. However, only 30-40% of patients had achieved HBsAg clearance after Peg-IFN α-2b administration. The biological targets and the underline mechanisms that distinguish sensitive and insensitive populations to interferon therapy are still unclear. In the present study, only 33.33% of patients achieved HBsAg loss after 48 weeks of Peg-IFN α-2b therapy. Thirty-six exosomal-microRNAs (miRNAs) in the sensitive group were identified that might induce sensitivity specifically, whereas 32 exosomal-miRNAs in the insensitive group were identified that might induce insensitive specifically. Among these miRNAs, five miRNAs (miR-425-5p, miR-8485, miR-619-5p, miR-181a-5p, and miR-484) might increase the sensitivity to Peg-IFN α-2b therapy by regulating key genes GSK3B, KRAS, FLT1, or GRB2, whereas, 13 miRNAs (miR-195-5p, miR-215-5p, miR-9-5p, miR-130a-3p, miR-214-3p, miR-149-5p, miR-429, miR-200b-3p, miR-200c-3p, miR-16-2-3p, miR-141-3p, miR-200a-3p, and miR-218-5p) might decrease the sensitivity to Peg-IFN α-2b therapy by regulating key genes, FGF2, GSK3B, PDGFRA, FGFR1, KRAS, FLT1, MYC, TGFB2, EFNA1, MAPK9, or GRB2. Furthermore, seven novel miRNAs, namely Novel_352, Novel_459, Novel_527, Novel_677, Novel_717, Novel_749, and Novel_801 were found to be downregulated specifically in the sensitive group, whereas, Novel_142 and Novel_664 were found to be downregulated specifically in the insensitive group. Our data indicate that the serum exosomal-miRNAs could be involved in regulating the sensitivity of chronic HBV (CHB) patients to Peg-IFN α-2b therapy, which might suggest potential novel therapeutic biomarkers and standard options for CHB patients. Clinical Trials.gov ID: NCT04035837.

THE DEVELOPMENT AND STUDY OF THE TOXICITY OF SUPPOSITORIES WITH A MODIFIED SUBSTANCE OF INTERFERON ALFA-2B

Objective: To develop a stable composition with the substance of PEGylated interferon alfa-2b, to study technological and biopharmaceutical characteristics of the dosage form, and to conduct preclinical studies on the chronic toxicity and local irritating effect. Methods: Solid fats Witepsol® H15, Witepsol® W 35, Suppocire® BS2X, and Suppocire® BM brands were used as the suppository bases. Polysorbate 80 was used as an emulsifier. Citric acid, ascorbic acid, sodium tetraborate, lactic acid, ethylenediaminetetetraacetic acid, tocopherol acetate was also introduced into the experimental samples. Fourteen experimental samples were screened for biological and technological indicators. Preclinical studies were performed for the optimal composition on the indicators of chronic toxicity and local irritant effect. Results: The study examined the cytotoxic effects on the Vero cell line of selected suppository bases and excipients, namely, pH regulators and antioxidants. With excipients that did not have cytotoxicity we obtained suppository compositions with the following quality indicators: cytotoxicity, specific activity of interferon, time of complete deformation of suppositories and their melting temperature. A total of 14 compositions were studied, of which 5 were selected on the basis of the results for the study of stability. Only one composition turned out to be stable for the time studied. Conclusion: The most stable in terms of “specific activity” was sample 7, its composition: Witepsol® H15/W35 70/30, polysorbate-80 0.15%, ethylenediaminetetraacetic acid (EDTA) 0.15%, sodium tetraborate 0.15%, tocopherol acetate 3.0%. Preclinical studies, that showed the absence of chronic toxicity and local irritant effect, were performed for this composition.

Effect of Lyophilization on Stability of PEG-Protein Conjugate: A Case Study with Peginterferon alfa-2b

Effect of Lyophilization on Stability of PEG-Protein Conjugate: A Case Study with Peginterferon alfa-2b

Efficacy and Safety of Peginterferon Alfa-2b in 95 Patients with Myeloproliferative Neoplasms:a Single Center Retrospective Analysis

Background Polycythemia vera (PV) and essential thrombocythemia (ET) are a common type of Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) driven by the JAK2,CALR or MPL mutation, which are associated with a reduced quality of life, a high rate of vascular events, and an intrinsic risk of disease evolution to myelofibrosis and acute myeloid leukemia. Pegylated interferon has obtained high-level evidence for short-term clinical trial endpoints such as hematocrit control, symptom burden/quality of life, splenomegaly, and JAK2 allele burden lies within the timeline of most studies. Objective To investigate the efficacy and safety of Peginterferon alfa-2b in patients with myeloproliferative neoplasms Methods The clinical data of 95 patients with MPNs treated with Peginterferon alfa-2b in Peking Union Medical College Hospital (Beijing, China) from January 2018 to May 2022 were retrospectively analyzed. Peginterferon alfa-2b was administered subcutaneously once weekly at a starting dose of 180ug, and could be decreased over time to 180ug every 2 to 4 weeks if hematological control was achieved. Hematological control was defined as HCT<45% in the absence of phlebotomy in patients with PV and PLT<400x109/L in patients with ET. Molecular response was defined as JAK2 allele burden decreased＞50% from baseline (partial remission) or undetectable at a lower limit of quantitation at 1% by the central laboratory (complete remission) which was measured by next-generation sequencing Results Among the 95 patients, 48 were male and 47 were female. There were 61 cases of PV and 34 cases of ET. The median age at diagnosis was 45 (17-69) years, and the median time from onset to diagnosis was 5.1 (0-413) months. All patients had next-generation sequencing for the driver mutations, there were 84 cases of JAK2 mutation, 8 cases of CALR mutation, 1 case of MPL mutation, and 2 cases of triple negative. The median duration of Peginterferon alfa-2b exposure was 13.2（2~51）months. 54 (88.5%) of 61 patients with PV achieved hematological control and 24 (70.6%) of 34 patients with ET achieved hematological control. The median onset of action was 1.4 (0.5-6.7) months. 47 patients with JAK2 mutation were detected with JAK2 allele burden for molecular evaluation. A total of 17 (36.2%) patients obtained molecular partial remission by 6 months and 26 (55.3%) patients achieved molecular partial remission by 12 months while no one achieved molecular complete remission. The most common treatment-emergent adverse events were influenza-like symptoms (88.4%), hyperglobulinemia (14.7%), elevated alanine aminotransferase (13.7%), and subclinical hypothyroidism (7.4%). A total of 4 patients (4.2%) discontinued the treatment, 2 due to intolerance of adverse effects, 1 due to disease progression to myelofibrosis, and 1 due to pregnancy. Conclusion This study demonstrates that Peginterferon alfa-2b was safe, well tolerated, and efficacious in patients with PV and ET. Keywords: Peginterferon alfa-2b, myeloproliferative neoplasms, hematological control molecular response

Comparison of the Efficacy and Safety of Pegylated Interferon Alpha-2b and Common Interferon Alpha in Patients with Myeloproliferative Neoplasms

Objective: To compare the efficacy and safety of pegylated interferon alpha-2b (PEG-IFN-α2b) and common interferon alfa (IFN-α) in the treatment of myeloproliferative neoplasms (MPNs). Methodology: This study was designed as a prospective clinical study. Patients with MPN who visited the Second Hospital of Tianjin Medical University from August 1, 2019 to June 30, 2022 were enrolled in this study. There were 30 patients in the PEG-IFN-α2b group and 60 patients in the common IFN-α group, and the median follow-up period was 24 (9 - 32) months. The differences in the clinical characteristics, efficacy and safety indicators between the two groups were compared. Results: ①The baseline clinical characteristics of patients in the PEG-IFN-α2b group and the common IFN-α group were well balanced and comparable. ②Efficacy: There was no significant difference in hematological objective response rate (ORR) at month 6, 12 and 24 between the PEG-IFN-α2b group and the common IFN-α group (68.2% vs 60%, 86.4% vs 68.3%, 84.6% vs 68.3%, P > 0.05); the ORR of molecular response at month 12 in the PEG-IFN-α2b group was higher than that in the common IFN-α group (81% vs 47.1%, P = 0.022); the proportion of patients with decreased V617F%and scores for MPN-10 symptoms in the PEG-IFN-α2b group was significantly higher than that in the common IFN-α group (80% vs 46.4%, 82.4% vs 44.2%, P < 0.05); Interleukin-6 (IL-6), Tumor necrosis factor alpha (TNFα) and Interferon gamma (IFNγ) in the PEG-IFN-α2b group after treatment were significantly lower than those before treatment (P < 0.05); the event-free survival (EFS) in the PEG-IFN-α2b group tended to be longer than that in the common IFN-α2b group, and for patients with essential thrombocythemia (ET), the EFS in the PEG-IFN-α2b group was significantly longer than that in the common IFN-α group (P < 0.05). ③Safety: There was no significant difference in the incidence of hematological toxicity between the two groups, and the incidence of grade 3-4 adverse events of fever and influenza-like symptoms as non-hematological toxicity was significantly lower than that in the common IFN-α group (6.6% vs 23.3%, 6.6% vs 15%, P < 0.05). Conclusion: Compared with common IFN-α group, PEG-IFN-α2b group showed significantly superior results for molecular response rate, V617F% reduction, physical symptoms improvement, and IL-6, TNFα and IFNγ reduction, as well as prolong EFS in ET patients with better safety profile. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A Phase 3 clinical trial validating the potency and safety of an innovative, extra-long-acting interferon in chronic hepatitis C.

Ropeginterferon alfa-2b is a novel mono-pegylated, extra-long-acting interferon. It is administered infrequently and showed good tolerability and clinical activity for the chronic hepatitis B or C treatment in our previous Phase 2 clinical trials. This study aims to validate the potency and safety of this novel agent in a Phase 3 chronic viral hepatitis setting. Patients with chronic hepatitis C genotype 2 were randomized to receive subcutaneous injections of ropeginterferon alfa-2b biweekly or the conventional pegylated interferon alfa-2b weekly for 24 weeks, combined with ribavirin. The primary endpoint was to assess the safety and antiviral potency of ropeginterferon alfa-2b by the non-inferiority in sustained virologic response at 12 weeks after treatment. A total of 222 patients were enrolled. Ropeginterferon alfa-2b group showed a favorable safety profile. Side effects that were generally associated with prior interferon therapies, including neutropenia, asthenia, fatigue, alopecia, dizziness, decreased appetite, nausea, flu-like symptoms including myalgia, pyrexia, and headache, and administration site reactions, were notably less in the ropeginterferon alfa-2b group. The cumulative incidence of adverse events of special interest was also notably higher in the control group. The primary endpoint was met and ropeginterferon alfa-2b showed a better SVR12 rate of 79.8% than 71.9% of the control group. Ropeginterferon alfa-2b is efficacious and has a favorable safety profile as compared with the conventional pegylated interferon alfa-2b. This study together with previous Phase 2 data validated ropeginterferon alfa-2b to be a new treatment option for chronic hepatitis C genotype 2.

Toxicity and bioactivity evaluation of interferon alpha-2b conjugated with solid lipid nanoparticles

Background: Interferon (IFN) are small proteins that belong to the cytokine family and may interfere with viral infections and some cancers. There are many studies focused on the PEGylated interferon’s bioactivity. In this study, we used solid lipid nanoparticles (SLNs) to produce new drug formulations, with the aim of reducing costs, increasing effectiveness, and also reducing side effects, and the biological effects of the formulation and comparing the obtained results with the interferon alpha-2b and PEGylated interferon alpha-2b.

Abstract 3577: First-in-human phase I study of intraperitoneally administered interferon-activated autologous monocytes in platinum-resistant ovarian cancer

Abstract Background: Ovarian cancer is the most lethal gynecologic cancer and is intrinsically resistant to immunotherapies. Previous work has demonstrated superior response rates with intraperitoneally (IP) directed therapies, providing the rationale for IP immunotherapy. Methods: A previously published model system in which OVCAR ovarian cancer spheroids are killed by IFN-activated human monocytes was further characterized using confocal microscopy, global gene expression analysis, flow cytometry, and knockout/knockdown of key genes in the TRAIL-DR4/DR5 pathway. These results were translated into a phase I dose escalation trial in which 3-6 patients with platinum-resistant or refractory ovarian cancer were enrolled into 4 cohorts and treated IP q28 days with Peginterferon alfa-2b (25-250 mcg) and Interferon gamma-1b (5-50 mcg), with or without autologous monocytes (75-750 x 106 cells), in order to determine the recommended phase II dose (RP2D). Results: Confocal microscopy of IFN-activated monocytes demonstrated migration into OVCAR spheroids and destruction of the spheroids and global gene expression analysis identified TRAIL as a ligand on monocytes upregulated by IFN treatment. Disruption of TRAIL receptors DR4/DR5 or deletion of CASPASE8 on OVCAR cells largely abrogated killing. IFN-activated human monocytes were able to kill IP-injected OVCAR tumor cells in a mouse xenograft model, and IFN-activated monocytes from ovarian cancer patients were able to kill OVCAR spheroids as effectively as those from healthy donors. 18 patients were subsequently enrolled on a phase I trial (median age, 61 years; median 5 prior therapies). 1 of 3 patients at the second dose level experienced a dose-limiting toxicity (grade 3 anemia) and no subsequent DLTs were observed. The RP2D was defined as 250mcg IFNa/50mcg IFNg/750 x 106 cells. The only treatment-related grade 3 or higher adverse events occurring in more than one patient were lymphocyte decrease (33.3%) and abdominal pain (11.1%). The best response observed was partial response (PR) in 2/9 RECIST-evaluable patients, and 1 additional patient had a CA-125 response with &amp;gt;50% reduction. 4/9 patients had stable disease. Four patients were able to receive 5+ cycles (range 1-10 cycles). Biomarker analyses demonstrated that these long-term responders had a lower level of T-regulatory cells at baseline, but exhibited marked increase in myeloid derived suppressor cells (MDSC) at the time of tumor progression. Conclusion: These findings characterize the mechanism of a novel cellular immunotherapy for ovarian cancer which is well tolerated with evidence of clinical activity in a heavily pretreated patient population. This therapy may serve as the backbone for a combination immunotherapy regimen incorporating additional agents targeting T-regulatory cells and/or MDSCs. Citation Format: Christopher B. Cole, Daniel S. Green, Franklin Ning, Kathryn Zoon, Lindsey B. Rosen, Steven M. Holland, Christina M. Annunziata. First-in-human phase I study of intraperitoneally administered interferon-activated autologous monocytes in platinum-resistant ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3577.

LGG-64. A Phase II Study of Pegylated Interferon in Children with Recurrent or Refractory and Radiographically or Clinically Progressive Juvenile Pilocytic Astrocytomas and Optic Pathway Gliomas (NCT02343224)

Unresectable Juvenile Pilocytic Astrocytomas (JPA) and Optic Pathway gliomas (OPG) are chronic diseases that can have solid +/- cystic components. We wanted to evaluate the objective response to pegylated interferon Alpha2B in this group of patients in a prospective single arm Phase II clinical trial. Eligibility criteria: age 3 -25 years, patients with neurofibromatosis (NF) were eligible, evidence of measurable disease in MRI, no limitation in the number of prior therapies including chemotherapy and radiation. Exclusion criteria: prior pegylated interferon exposure, less than 2 years from radiation, active autoimmune disease. Subjects enrolled received pegylated interferon 1 mcg/kg/dose SQ weekly, to a max dose of 150mcg/dose in 28 day cycles for up to 2 years. The study design is a Simon two stage design. If no complete or partial responses among the first 9 patients, the study will terminate. Nine subjects enrolled: 4 females, 5 males, median age of 11years, 6 Caucasians, 3 African Americans. Two subjects with NF. Molecular findings KIAA-BRAF fusion (6), V600E mutation (1), CDK2A loss (1). Location: brain (7), brain and spine (2). We enrolled a heavily pre-treated population, patients with prior radiation ( 1), nine with prior chemotherapy, the average number of regimens 4 (range 2-6). No complete responses or partial responses were seen. Two patients with prolonged stable disease 75+months and 66+ months. At 12 and 24 month EFS 76.2% (95%CI52.1-100%). Median EFS has not been reached. The 12 and 24 months survival estimate 75% (95% CI 50.3-100%), median survival has not been reached. Side effects as expected mostly grade 1-2. No grade 4 event related to pegylated interferon were seen. This is the first report of pegylated interferon in OPG and JPA, two patients with prolonged stable disease suggesting that pegylated interferon can offer potential benefit in this population and additional studies are important.

Epidemiology and Natural History of Childhood-Acquired Chronic Hepatitis C: A Single-Center Long-Term Prospective Study.

To prospectively describe the epidemiology and long-term outcome of childhood-acquired hepatitis C virus (HCV) infection in a large cohort of children followed at a single center. All children with chronic HCV infection followed at the Liver Unit of our tertiary Hospital in Florence (Italy) from January 1, 1988, to September 30, 2021, were included in the analysis. The final sample consisted of 163 children (median age at enrollment 4 years, interquartile range (IQR): 10; median age at last follow-up 14 years, IQR: 7). The median duration of follow-up was 86 months (IQR: 112). One hundred twenty-five children were vertically infected and 26 acquired the infection horizontally. Twenty-six of the 125 children who were vertically infected (20.8%) underwent spontaneous clearance of HCV RNA at a median age of 4 years (IQR: 2), whereas all the others remained persistently viremic. One patient was diagnosed with cirrhosis; 2 presented clinically detectable extrahepatic manifestations (chronic urticaria). Thirty-two children (19.6%) received antiviral therapy: 8 out of 32 (25%) were treated with pegylated-interferon alfa-2b [sustained virological response (SVR) 24 weeks after the end of treatment in 7/8]; 24 out of 32 (75%) were treated with direct-acting antivirals (SVR 12 weeks after the end of treatment in 23/24). The present study describes the largest cohort of children with chronic HCV infection prospectively evaluated with a long follow-up at a single center. HCV infection in children is often a chronic infection that can be cured with modern antiviral therapy. Early treatment could prevent the development of advanced liver disease.

Outcome of Treatment in Children With Chronic Viral Hepatitis C: A Single Centre Study.

ObjectiveTo review the efficacy of the combination of pegylated interferon-α 2b and ribavirin, and sofosbuvir and ribavirin in achieving sustained viral response (SVR) in chronic hepatitis C genotypes 1 and 3 in children.MethodsA retrospective descriptive study was performed for children under 15 years of age treated for chronic hepatitis C at Pakistan Kidney and Liver Institute and Research Centre, Lahore, between 2018 and 2019. Demographic data and clinical information were collected. In addition, treatment outcome was assessed by SVR, defined as the absence of detectable viral RNA in blood after 24 weeks of initiation of treatment.ResultsA total of 30 children aged 15 years and below were included in this study. Sixteen of 30 children were males, and 14 were females. Of these 30 patients, four had hepatitis C virus (HCV) genotype 1, and 26 children had HCV genotype 3. The children with genotype 1 (a+b) were given the combination of ribavirin and pegylated interferon alfa-2b (Peg-IFN-α-2b). The remaining with HCV genotype 3 were given the combination of ribavirin and sofosbuvir for 24 weeks. Overall, 27 out of 30 (90%) children attained SVR at six months (100% children with genotype 1 and 88.4% children with genotype 3).ConclusionThe combined therapy of ribavirin and sofosbuvir or Peg-IFN-α-2b and ribavirin is highly effective in treating chronic HCV infection in children.

Pegylated Interferon Alpha-2b in Patients With Polycythemia Vera and Essential Thrombocythemia in the Real World.

Several clinical trials have shown promising efficacy of pegylated interferon (Peg-IFN) in the first- and second-line polycythemia vera (PV) and essential thrombocythemia (ET). However, the efficacy and safety of Peg-IFN in the real world have rarely been reported. Hence, we conducted a prospective, single-center, single-arm, open exploratory study, which aimed to explore the hematologic response, molecular response, safety, and tolerability of patients with PV and ET treated with Peg-IFN in the real world. This study included newly diagnosed or previously treated patients with PV and ET, aged 18 years or older, admitted to the Department of Hematology of the First Affiliated Hospital of Soochow University from November 2017 to October 2019. The results revealed that complete hematological response (CHR) was achieved in 66.7% of patients with PV and 76.2% of patients with ET, and the molecular response was obtained in 38.5% of patients with PV and 50% of patients with ET after 48 weeks of Peg-IFN treatment. Peg-IFN is safe, effective and well tolerated in most patients. In the entire cohort, 4 patients (9.1%) discontinued treatment due to drug-related toxicity. In conclusion, Peg-IFN is a promising strategy in myeloproliferative neoplasms (MPNs), and Peg-IFN alone or in combination with other drugs should be further explored to reduce treatment-related toxicity and improve tolerability.