PKPD Assessment of the Anti-CD20 Antibody Obinutuzumab in Cynomolgus Monkey is Feasible Despite Marked Anti-Drug Antibody Response in This Species. | LitMetric
The pharmacokinetics (PK) of the anti-CD20 monoclonal antibody obinutuzumab was assessed after single intravenous dosing to cynomolgus monkeys. In addition, the pharmacokinetic-pharmacodynamic (PKPD) relationship for B-cell depletion was characterized. The PKPD model was used to estimate the B-cell repopulation during the recovery phase of chronic toxicology studies, thereby supporting the study design, in particular planning the recovery phase duration. Marked immunogenicity against obinutuzumab was observed approximately 10 days after single dose, leading to an up to ∼30-fold increase in obinutuzumab clearance in the affected monkeys. Despite this accelerated clearance, the PK could be characterized, either by disregarding the clearance in noncompartmental PK analysis or by capturing it explicitly as an additional time-dependent clearance process in compartmental modeling. This latter step was crucial to model the PKPD of B-cells as an indirect response to obinutuzumab exposure, showing that-without immune response-the limiting factor is obinutuzumab elimination with concentrations below 0.02 μg/mL required for initiation of B-cell recovery. Overall, the results demonstrate that despite a marked anti-drug antibody response in the nonclinical animal species, the PK and PKPD of obinutuzumab could be characterized successfully by appropriately addressing the immune-modulated clearance pathway in data analysis and modeling.
The prevalence of anti-CD20 monoclonal antibody (MoAb)-associated delayed-onset neutropenia (DON) varies between 8 and 27%. Despite the wide use of MoAbs as maintenance in follicular lymphoma (FL), data regarding DON occurrence and clinical consequences are limited. This study assessed DON prevalence, severity and risk factors in FL patients during maintenance.
Obinutuzumab has been widely used in patients with CD20 positve B-cell non-Hodgkin's lymphoma for more than 10 years since its launch, bringing significant clinical benefits. At present, studies at home and abroad have confirmed that the 90-minute short duration infusion of obinutuzumab is safe and feasible.In order to improve the convenience of patient infusion and the efficiency of medical institutions'infusion facilities, it is recommended for patients who do not experience grade ≥3 infusion-related adverse reactions in the first cycle of obinutuzumab infusion at the standard rate, a short duration infusion scheme should be used for subsequent treatment courses.
Objectives: Dysregulation of Epstein-Barr virus (EBV)-specific cellular immunity has been hypothesised as one of the contributing factors in the pathogenesis of systemic lupus erythematosus (SLE). Lupus nephritis is a major risk factor for overall morbidity in SLE. Immune-based strategies directed to EBV have been proposed as potential therapeutic strategy for SLE and lupus nephritis.
Background: Obinutuzumab is a humanized and glycoengineered anti-CD20 monoclonal antibody that has been shown to induce more profound B-cell depletion than rituximab. The effectiveness and safety of obinutuzumab in the treatment of membranous nephropathy remain unclear.
Methods: This was a retrospective study conducted in Huashan Hospital, Fudan University between 1 December 2021 and 30 November 2023.
Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, Yonago City, Tottori, Japan.
A 68-year-old woman with follicular lymphoma was treated with chemotherapy, including the anti-CD20 monoclonal antibody obinutuzumab, and achieved remission. A month after the administration of obinutuzumab, the patient contracted coronavirus disease 2019 (COVID-19), and various antiviral drugs were administered. However, the infection had not been eliminated.
