ArticleBritish journal of clinical pharmacology2012
Model-based design of rituximab dosage optimization in follicular non-Hodgkin's lymphoma.
Article in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Non-Linear Rituximab Pharmacokinetics and Complex Relationship between Rituximab Concentrations and Anti-Neutrophil Cytoplasmic Antibodies (ANCA) in ANCA-Associated Vasculitis: The RAVE Trial Revisited.Clinical pharmacokinetics · 2020Trial
- Inebilizumab reduces neuromyelitis optica spectrum disorder risk independent of FCGR3A polymorphism.Annals of clinical and translational neurology · 2023Article
- Obinutuzumab in the treatment of B-cell malignancies: a comprehensive review.Future oncology (London, England) · 2022Review
- Mechanisms of Resistance to Monoclonal Antibodies (mAbs) in Lymphoid Malignancies.Current hematologic malignancy reports · 2019Review
- Monitoring B-cell repopulation after depletion therapy in neurologic patients.Neurology(R) neuroimmunology & neuroinflammation · 2018Article
- Review
- Obinutuzumab for the treatment of patients with previously untreated chronic lymphocytic leukemia: overview and perspective.Therapeutic advances in hematology · 2015Review
- Germline oncopharmacogenetics, a promising field in cancer therapy.Cellular oncology (Dordrecht, Netherlands) · 2015Review
- A new frontier in haematology - combining pharmacokinetic with pharmacodynamic factors to improve choice and dose of drug.British journal of clinical pharmacology · 2014Review
- Pharmacokinetics, pharmacodynamics and physiologically-based pharmacokinetic modelling of monoclonal antibodies.Clinical pharmacokinetics · 2013Review
- Review
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
what is already known about this subjectThe concentration-effect relationship of rituximab in follicular lymphoma (FL) was previously described using pharmacokinetic-pharmacodynamic (PK-PD) modelling. The influence of genetic polymorphism of FCGR3A on rituximab efficacy in FL patients was included in this PK-PD model. Previous studies suggest that increasing the dose of rituximab and/or the number of infusions may lead to a better clinical response in FL. WHAT THIS STUDY ADDS: The previously validated PK-PD model can be used to design an optimized rituximab dose regimen in FL patients. Clinical trial simulation shows the potential clinical benefits of changes in rituximab dose. Optimization of the rituximab dose regimen cannot compensate for the lower response of FCGR3A-158F carriers compared with that of FCGR3A-158VV patients. AIMS Rituximab has dramatically improved the survival of patients with non-Hodgkin's lymphoma (NHL). However, studies have suggested that the dose regimen currently used (i.e. 375 mg m(-2) ) could be optimized. The aims of this study were to quantify the benefits of the new dose regimen for rituximab in follicular NHL (FL) patients using a previously validated PK-PD model and to design clinical trials investigating optimization of rituximab dosage.
methodsA PK-PD model was used to predict progression-free survival (PFS) of FL patients treated by rituximab alone in asymptomatic FL, and those treated by rituximab combined with chemotherapy (R-CHOP) in relapsed/resistant FL. This model accounts for the influence of a polymorphism in FCGR3A, the gene encoding the FcγRIIIa receptor, on clinical efficacy. Several induction and maintenance dose regimens using rituximab alone or in combination with conventional chemotherapy (CHOP) were tested. The benefits of rituximab dose adjustment for F carriers were investigated. The numbers of subjects required for the design of two-armed clinical trials were calculated using model-predicted PFS at a power of 80%.
resultsThe model predicted a potential benefit of 1500 mg m(-2) maintenance doses of rituximab for both rituximab monotherapy and R-CHOP. The model shows that the PFS of FCGR3A-F carriers remains lower than that of homozygous FCGR3A-VV patients, even with markedly increased rituximab doses.
conclusionOur results suggest a benefit of increasing doses of rituximab in FL, both during induction and maintenance. These results need to be confirmed in controlled clinical trials.
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