Population pharmacokinetics of Reditux™, a biosimilar Rituximab, in diffuse large B-cell lymphoma

Cancer Chemother Pharmacol. 2016 Aug;78(2):353-9. doi: 10.1007/s00280-016-3083-x. Epub 2016 Jun 21.

Abstract

Purpose: Rituximab (MabThera™, Roche) is a chimeric IgG1 monoclonal antibody targeting the CD20 surface antigen on normal and neoplastic B cells. It revolutionized the treatment of non-Hodgkin's lymphoma with superior progression-free and overall survival. However, its prohibitively high cost makes it inaccessible to majority of patients in developing countries. Reditux™ (Dr. Reddy's Laboratories, India), a biosimilar, was introduced in India in 2007 at nearly half the price of the innovator. However, there is a dearth of data regarding the pharmacokinetics and efficacy of Reditux™.

Methods: Twenty-one patients of diffuse large B-cell lymphoma on R-CHOP regimen were enrolled for the study. Reditux™ was administered as a slow intravenous infusion at a dose of 375 mg/m(2) on day 1 of a 21-day cycle. Pharmacokinetic sampling was performed at pre-dose, post-infusion, 24, 48 h, 7 and 21 days. Rituximab levels were estimated by ELISA. Population pharmacokinetics was performed using NONMEM. In addition, B-cell count was determined at baseline and days 3 and 21 of the first cycle. Survival analysis was performed using Kaplan-Meier plots.

Results: The volume of distribution of central compartment and clearance of Reditux™ were estimated at 0.95 L and 5.98 mL/h, respectively. No covariate effects were seen. B-cell count was completely depleted by day 3 and remained so on day 21. Overall survival was 84.6 % at a median follow-up of 36 months.

Conclusion: The pharmacokinetic profile and B-cell response to Reditux™ are comparable with those reported for MabThera™. Thus, MabThera™ can be substituted with Reditux™ for the treatment of B-cell lymphomas.

Keywords: Biosimilar; DLBCL; MabThera; Population pharmacokinetics; Reditux; Rituximab.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / pharmacokinetics
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
  • Biosimilar Pharmaceuticals / administration & dosage*
  • Biosimilar Pharmaceuticals / pharmacokinetics
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacokinetics
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacokinetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Male
  • Middle Aged
  • Nonlinear Dynamics
  • Prednisone / administration & dosage
  • Prednisone / pharmacokinetics
  • Prospective Studies
  • Rituximab / administration & dosage*
  • Rituximab / pharmacokinetics
  • Survival Rate
  • Time Factors
  • Vincristine / administration & dosage
  • Vincristine / pharmacokinetics
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biosimilar Pharmaceuticals
  • R-CHOP protocol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • Prednisone