Exposure-efficacy and exposure-safety analyses of ropeginterferon alfa-2b treatment in patients with polycythaemia vera.

AIMS: To investigate the exposure-response (E-R) relationship, including exposure-efficacy and exposure-safety, of ropeginterferon alfa-2b treatment in patients with polycythaemia vera (PV). METHODS: Based on the results of the phase II trial A20-202 regarding ropeginterferon alfa-2b in patients with PV, E-R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E-R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa-2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment-related adverse events (TRAEs). RESULTS: A clear relationship between the exposure to ropeginterferon alfa-2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure-JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa-2b and baseline body surface area. Exposure-safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. CONCLUSIONS: Our analyses have shown that patients with PV treated with ropeginterferon alfa-2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250-350-500 µg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa-2b for PV treatment in China.

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

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

A phase II trial to assess the efficacy and safety of ropeginterferon α-2b in Chinese patients with polycythemia vera.

Ropeginterferon α-2b is a mono-PEGylated proline-interferon for the treatment of polycythemia vera. This drug is used biweekly with a starting dose of 100 µg (50 µg if patients receiving hydroxyurea) and 50 µg increments up to a maximum dose of 500 µg. Increasing evidence indicates that patients can tolerate higher starting doses of ropeginterferon α-2b. This phase II trial utilizes 250 µg as the starting dose, 350 µg at week 2 and 500 µg at week 4 as the target dose. Doses can be adjusted according to tolerability. This study assesses the safety, efficacy and molecular response of ropeginterferon α-2b in Chinese patients with PV utilizing the 250-350-500 µg dosing schema. This study will be used to support the application of a biologics license for polycythemia vera treatment in China.

Polycythemia vera (PV) is a slow-growing blood neoplasm (cells that grow and divide more than they should or do not die when they should). PV often has a mutation in the gene called JAK2, which causes changes in the DNA of genes that cause cells to become cancerous. PV is associated with an increased number of blood cells, debilitating symptoms, risks of thrombosis (blood clot) and bleeding and can progress to other diseases, including myelofibrosis and acute myeloid leukemia. Ropeginterferon α-2b is a new product with favorable properties, allowing a convenient dosing schedule of every 2­4 weeks. This drug has demonstrated good tolerability, safety and efficacy for PV treatment and has been approved for the treatment of PV in Europe and the USA. This article discusses the design of an ongoing study that looks at the safety and efficacy of ropeginterferon α-2b for the treatment of PV. The study follows a specific dosing schedule, with the aim of controlling the neoplasm faster, and plans to include 49 patients from 12­15 major hospitals in China. Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (identifier: NCT05485948) and in China (China National Medical Products Administration Clinical Trial Registration Number: CTR20211664).

[Serum levels of tumor necrosis factor α and interferon γ in patients with hemophagocytic syndrome and its clinical significance].

In order to explore the serum levels and clinical significance of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in patients with hemophagocytic syndrome (HPS). The clinical data of HPS patients in Capital Medical University Beijing Friendship Hospital from October 2008 to October 2010 were collected. The serum concentration of TNF-α and IFN-γ in HPS patients and 20 healthy controls was measured with enzyme-linked immunosorbent assay (ELISA). The correlations between the levels of TNF-α and primary disease were analyzed, the levels of hemoglobin, ferritin, triglyceride, NK cell activity and sCD25 were detected on the same day, the correlations between the concentrations of TNF-α and IFN-γ and these laboratory indicators were analyzed. The results indicated that the serum levels of TNF-α and IFN-γ in 30 cases of HPS was higher than that in control group (p < 0.05, p < 0.01); the difference of TNF-α concentration was statistically significant in rheumatism-related and tumor-related HPS groups(p = 0.04), the level of TNF-α in HPS patients showed negative correlation with hemoglobin. It is concluded that the high levels of TNF-α and IFN-γ in HPS patients may play certain roles in the pathogenesis and progress of HPS. These data indicated that the high level of TNF-α may be the main factor for anemia in patients with HPS.

[Expression of serum sHLA-G in patients with hemophagocytic syndrome and its clinical significance].

In order to investigate the expression of serum sHLA-G in hemophagocytic syndrome (HPS) patients and to evaluate its clinical significance, the clinical data of HPS patients in Capital Medical University Beijing Friendship Hospital during the period from September 2008 to July 2010 were collected. They were divided into infection-associated HPS, tumor-associated HPS and rheumatological disease-associated HPS according to cause of diseases. The serum concentration of sHLA-G in HPS patients and 25 healthy controls was measured by enzyme-linked immunosorbent assay (ELISA), the correlations between sHLA-G level and laboratory indicators were analyzed. The results showed that the level of serum sHLA-G in HPS patients was significantly higher than that in healthy controls (p = 0.003), but the difference was not statistically significant between HPS groups of different causes (p = 0.233). The positive correlation of sHLA-G level in HPS patients with platelet count was found, but there was no positive correlation of their sHLA-G levels with WBC, Hb, Plt, ALT, AST, LDH, Alb, TBil, DBil, IBil, Cr, BUN, TG, fibrinogen and ferritin levels detected on same day. It is concluded that the the increase of serum sHLA-G levels in HPS patients may be caused by different factors such as infection, tumor, T cell activation and over-stimulation of several cytokines. sHLA-G can inhibit NK cell activity, resulting in formation of abnormal immune storm, and may be play a role in the pathogenesis of HPS.