{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:00:18Z","timestamp":1791262818450,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,12]],"date-time":"2012-03-12T00:00:00Z","timestamp":1331510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003The concentration\u2013effect relationship of rituximab in follicular lymphoma (FL) was previously described using pharmacokinetic\u2013pharmacodynamic (PK\u2013PD) modelling.<\/jats:p><jats:p>\u2022\u2003The influence of genetic polymorphism of <jats:italic>FCGR3A<\/jats:italic> on rituximab efficacy in FL patients was included in this PK\u2013PD model.<\/jats:p><jats:p>\u2022\u2003Previous studies suggest that increasing the dose of rituximab and\/or the number of infusions may lead to a better clinical response in FL.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003The previously validated PK\u2013PD model can be used to design an optimized rituximab dose regimen in FL patients.<\/jats:p><jats:p>\u2022\u2003Clinical trial simulation shows the potential clinical benefits of changes in rituximab dose.<\/jats:p><jats:p>\u2022\u2003Optimization of the rituximab dose regimen cannot compensate for the lower response of <jats:italic>FCGR3A\u2010158F<\/jats:italic> carriers compared with that of <jats:italic>FCGR3A\u2010158VV<\/jats:italic> patients.<\/jats:p><jats:p><jats:bold>AIMS<\/jats:bold> Rituximab has dramatically improved the survival of patients with non\u2010Hodgkin's lymphoma (NHL). However, studies have suggested that the dose regimen currently used (i.e. 375\u2003mg\u2003m<jats:sup>\u22122<\/jats:sup>) 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\u2013PD model and to design clinical trials investigating optimization of rituximab dosage.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> A PK\u2013PD model was used to predict progression\u2010free survival (PFS) of FL patients treated by rituximab alone in asymptomatic FL, and those treated by rituximab combined with chemotherapy (R\u2010CHOP) in relapsed\/resistant FL. This model accounts for the influence of a polymorphism in <jats:italic>FCGR3A<\/jats:italic>, the gene encoding the Fc\u03b3RIIIa 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\u2010armed clinical trials were calculated using model\u2010predicted PFS at a power of 80%.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> The model predicted a potential benefit of 1500\u2003mg\u2003m<jats:sup>\u22122<\/jats:sup> maintenance doses of rituximab for both rituximab monotherapy and R\u2010CHOP. The model shows that the PFS of <jats:italic>FCGR3A\u2010F<\/jats:italic> carriers remains lower than that of homozygous <jats:italic>FCGR3A<\/jats:italic>\u2010VV patients, even with markedly increased rituximab doses.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold> Our results suggest a benefit of increasing doses of rituximab in FL, both during induction and maintenance. 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