Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods: This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 × 109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50 × 109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50 × 109/L or ≥100 × 109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30 × 109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings: From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT ≥50 × 109/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50 × 109/L or ≥100 × 109/L or an increase twice more than baseline as well as ≥30 × 109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates. Interpretation: This study preliminarily confirmed that 100 mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. Funding: National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

The Clinical Value of Systemic Immune Inflammation Index (SII) in Predicting the Severity of Hospitalized Children with Mycoplasma Pneumoniae Pneumonia: A Retrospective Study.

Objective: The Systemic Immune Inflammation Index (SII), as a novel inflammation biomarker that comprehensively reflects the inflammatory and immune status of the body, has not been reported in studies on Mycoplasma pneumoniae pneumonia (MPP) in children. This study aims to investigate whether SII can serve as an effective indicator for evaluating the condition of MPP. Methods: This study recruited a total of 304 hospitalized patients with mycoplasma pneumoniae pneumonia (MPP), including 78 patients with severe MPP (SMPP) and 226 patients with non-SMPP. Univariate analysis using chi-square test, t-test, and Mann-Whitney U-test was conducted to analyze the clinical data of the patients. Logistic regression analysis was employed to identify the main risk factors for SMPP. Receiver operating characteristic curves were plotted to evaluate the potential of using neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic immune response index (SIRI) to predict the severity of MPP. Results: The ROC curve results show that patients with SII values ≥ 699.00 are more likely to develop severe MPP (sensitivity=0.876, specificity=0.987, AUC=0.940), and the predictive value of SII is significantly better than that of NLR, PLR, and SIRI. The results of multivariate logistic regression analysis indicate that SII can serve as a major risk factor for distinguishing non-SMPP from SMPP. Conclusion: This study suggests that SII may be an effective indicator for predicting the severity of MPP in children. SII is more sensitive and specific than NLR, PLR, and SIRI in evaluating the condition of MPP.

[Functional mechanisms of WRKY transcription factors in regulating plant response to abiotic stresses].

WRKYs is a unique family of transcription factors (TFs) in plants, and belongs to the typical multifunctional regulator. It is involved in the regulation of multiple signaling pathways. This type of transcription factor is characterized to contain about 60 highly conservative amino acids as the WRKY domain, and usually also has the Cys2His2 or Cys2His-Cys zinc finger structure. WRKYs can directly bind to the W-box sequence ((T)(T) TGAC (C/T)) in the promoter region of the downstream target gene, and activate or inhibit the transcription of the target genes by interacting with the target protein. They may up-regulate the expression of stress-related genes through integrating signal pathways mediated by abscisic acid (ABA) and reactive oxygen species (ROS), thus playing a vital role in regulating plant response to abiotic stresses. This review summarizes the advances in research on the structure and classification, regulatory approach of WRKYs, and the molecular mechanisms of WRKYs involved in response to drought and salt stresses, and prospects future research directions, with the aim to provide a theoretical support for the genetic improvement of crop in response to abiotic stresses.