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

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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/m2 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.

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Acknowledgments

This clinical study protocol was designed at the Asia Pacific Clinical Oncology Research and Development (ACORD) Workshop in 2010. The authors are grateful to the ACORD faculty for their guidance. The authors also extend gratitude to the Tata Memorial Centre Intramural Grant for providing financial support.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Navi Mumbai, 410210, India

    Vikram Gota, Ashwin Karanam, Sanhita Rath & Akanksha Yadav

  2. Department of Pathology, Tata Memorial Hospital, Mumbai, 400012, India

    Prashant Tembhare & P. Subramanian

  3. Department of Medical Oncology, Tata Memorial Hospital, Mumbai, 400012, India

    Manju Sengar, Reena Nair & Hari Menon

  4. Department of Clinical Hematology, Tata Medical Center, Kolkata, 700156, India

    Reena Nair

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  1. Vikram Gota
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Correspondence to Vikram Gota.

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Gota, V., Karanam, A., Rath, S. et al. Population pharmacokinetics of Reditux™, a biosimilar Rituximab, in diffuse large B-cell lymphoma. Cancer Chemother Pharmacol 78, 353–359 (2016). https://doi.org/10.1007/s00280-016-3083-x

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  • DOI: https://doi.org/10.1007/s00280-016-3083-x

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