title: Is rituximab sub-optimally dosed in indolent B cell lymphoma?
abstract: Rituximab pharmacokinetics are affected by gender, age and weight and can affect outcomes in aggressive B cell lymphoma. Less is known about the pharmacokinetics of rituximab in indolent B cell lymphoma (iNHL). We analysed the effects of gender, age, weight and body surface area on the outcomes of 303 patients treated with first line rituximab-based regimens for iNHL. The patients were divided into 3 treatment cohorts: rituximab only, rituximab + chemotherapy (R-CTX) and R-CTX followed by rituximab maintenance; furthermore, each cohort was subdivided as follicular (FL) or non-FL, based on histology. Older males and patients with higher weight had worse outcomes when treated with R-CTX, probably due to faster rituximab clearance. Our results concur with studies of R-CTX for DLBCL. As this effect was not observed in patients treated with rituximab alone or R-CTX followed by rituximab maintenance, we hypothesize that higher rituximab levels reached with weekly rituximab and/or prolonged exposure achieved with maintenance therapy exceed the therapeutic threshold, even with faster clearance, which nullifies the negative effect of higher weight and male gender. In conclusion, under current practices, a subset of patients with iNHL, i.e., FL treated with R-CTX, may be sub-optimally dosed with rituximab.
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Yazeed
authors.identifier: 0000-0001-6355-3671
authors.initials: Y
authors.lastname: Sawalha
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Basel
authors.initials: B
authors.lastname: Rouphail
authors.affiliation: Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Dean
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Hill
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Deepa
authors.initials: D
authors.lastname: Jagadeesh
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Brad L
authors.initials: BL
authors.lastname: Pohlman
authors.affiliation: Department of Medical Oncology and Hematology, Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: Smith
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001835:Body Weight; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008224:Lymphoma, Follicular / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012737:Sex Factors
chemical_list: D000069283:Rituximab
keywords: body surface area; dosing; indolent lymphoma; pharmacokinetics; rituximab