Is rituximab sub-optimally dosed in indolent B cell lymphoma?

Br J Haematol. 2016 Sep;174(5):721-9. doi: 10.1111/bjh.14114. Epub 2016 May 2.

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.

Keywords: body surface area; dosing; indolent lymphoma; pharmacokinetics; rituximab.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Body Weight
  • Cohort Studies
  • Female
  • Humans
  • Lymphoma, B-Cell / drug therapy*
  • Lymphoma, Follicular / drug therapy
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Retrospective Studies
  • Rituximab / administration & dosage*
  • Rituximab / pharmacokinetics
  • Sex Factors

Substances

  • Rituximab