Real-world use and acceptance of rituximab biosimilars in non-Hodgkin lymphoma in an oncologist network in Germany
Abstract
Aim: Present real-world data for rituximab (biosimilar and reference)-containing regimens in extrapolated indications in non-Hodgkin lymphoma (NHL)/chronic lymphocytic leukemia (CLL). Patients & methods: Data collected from office-based oncologic practices in Germany (July 2017–June 2019). Results: Of 1741 patients, 1241 had NHL; 500 had CLL. Of 7595 therapy cycles, 28.3% used reference rituximab; 55.2% used rituximab biosimilars; 2.0% used subcutaneous rituximab; 14.5% used rituximab, not otherwise specified. Rituximab biosimilars were used across all indications; 57.3% of cycles were administered in extrapolated indications. Over 24 months, the proportion of rituximab prescriptions that were for biosimilars increased from 12.0 to 83.0%. Conclusion: Our real-world data in NHL and CLL depicts increasing use of rituximab biosimilars across multiple treatment protocols, including extrapolated indications.
Papers of special note have been highlighted as: • of interest; •• of considerable interest
References
- 1. Rituximab: the first monoclonal antibody approved for the treatment of lymphoma. Curr. Pharm. Biotechnol. 1(1), 1–9 (2000). •• A comprehensive summary of the development and use of rituximab across lymphoma indications.
- 2. ESMO Guidelines Committee. Appendix 4: Chronic lymphocytic leukaemia: eUpdate published online 27 June 2017 (www.esmo.org/Guidelines/Haematological-Malignancies). Ann.Oncol. 28(Suppl. 4), iv149–iv152 (2017).
- 3. . Assessment report: Rixathon (2017). www.ema.europa.eu/en/documents/assessment-report/rixathon-epar-public-assessment-report_en.pdf
- 4. . Truxima EPAR (2016).
- 5. . Rituximab biosimilars open new horizons in immunotherapy. ESMO Open 2(3), e000234 (2017).
- 6. . Rituximab biosimilars for lymphoma in Europe. Expert Opin. Biol. Ther. 19(10), 1045–1056 (2019). •• A concise up-to-date overview of approved and pipeline rituximab biosimilars, including detailed overviews of clinical development programs.
- 7. . Physicochemical and functional comparability between the proposed biosimilar rituximab GP2013 and originator rituximab. BioDrugs 27(5), 495–507 (2013).
- 8. Target-directed development and preclinical characterization of the proposed biosimilar rituximab GP2013. Leuk. Lymphoma 55(7), 1609–1617 (2014).
- 9. Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study. Lancet. Haematol. 4(8), e350–e361 (2017).
- 10. Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study. Ann. Rheum. Dis. 77(2), 234–240 (2018).
- 11. Brief report: safety and immunogenicity of rituximab biosimilar gp 2013 after switch from reference rituximab in patients with active rheumatoid arthritis. Arthritis Care Res. (Hoboken) 71(1), 88–94 (2019).
- 12. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol. 4(8), e362–e373 (2017).
- 13. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 in comparison with rituximab in patients with previously untreated low-tumour-burden follicular lymphoma: a randomised, double-blind, parallel-group, phase 3 trial. Lancet Haematol. 5(11), e543–e553 (2018).
- 14. A multicentre randomised controlled trial to compare the pharmacokinetics, efficacy and safety of CT-P10 and innovator rituximab in patients with rheumatoid arthritis. Ann. Rheum. Dis. 76(3), 566–570 (2017).
- 15. Efficacy, safety and pharmacokinetics of up to two courses of the rituximab biosimilar CT-P10 versus innovator rituximab in patients with rheumatoid arthritis: results up to week 72 of a Phase I randomized controlled trial. BioDrugs 31(4), 357–367 (2017).
- 16. Comparison of biosimilar CT-P10 and innovator rituximab in patients with rheumatoid arthritis: a randomized controlled Phase 3 trial. MAbs 10(6), 934–943 (2018).
- 17. Efficacy and safety of switching from innovator rituximab to biosimilar CT-P10 compared with continued treatment with CT-P10: Results of a 56-week open-label study in patients with rheumatoid arthritis. BioDrugs 31(4), 369–377 (2017).
- 18. A randomised, double-blind trial to demonstrate bioequivalence of GP2013 and reference rituximab combined with methotrexate in patients with active rheumatoid arthritis. Ann. Rheum. Dis. 76(9), 1598–1602 (2017).
- 19. . Scientific rationale underpinning the development of biosimilar rituximab in hematological cancers and inflammatory diseases. Future Oncol. 15(36), 4223–4234 (2019). • Uses data from the development process for a particular rituximab biosimilar to illustrate the overall principles of biosimilar development.
- 20. . Worldwide experience with biosimilar development. MAbs 3(2), 209–217 (2011).
- 21. . A clinician's guide to biosimilars in oncology. Cancer Treat Rev. 46, 73–79 (2016).
- 22. Biosimilars: what clinicians should know. Blood 120(26), 5111–5117 (2012). •• A straightforward introduction to biosimilar concepts, from development to approval.
- 23. Regulatory and clinical considerations for biosimilar oncology drugs. Lancet Oncol. 15(13), e594–e605 (2014).
- 24. . Biosimilars: the science of extrapolation. Blood 124(22), 3191–3196 (2014).
- 25. Rituximab in routine care of severe active rheumatoid arthritis: a prospective, non-interventional study in Germany. Z Rheumatol. 78(9), 881–888 (2019).
- 26. Diffuse large B-cell lymphoma: 10 years' real-world clinical experience with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone. Oncol. Lett. 15(3), 3602–3609 (2018).
- 27. Rituximab in combination with chemotherapy for the treatment of chronic lymphocytic leukaemia in clinical practice. Eur. J. Haematol. 100(5), 455–464 (2018).
- 28. Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study. Leuk. Lymphoma 58(6), 1366–1375 (2017).
- 29. Rituximab in patients with rheumatoid arthritis in routine practice (GERINIS): six-year results from a prospective, multicentre, non-interventional study in 2,484 patients. Arthritis Res. Ther. 16(2), R80 (2014).
- 30. . Real-world evidence studies (2015). www.appliedclinicaltrialsonline.com/real-world-evidence-studies
- 31. . “Evidence” trail elusive (2014) www.appliedclinicaltrialsonline.com/evidence-trail-elusive-0
- 32. . Comparative analysis of biosimilar rituximab usage in treating non-Hodgkin lymphoma and rheumatoid arthritis: results from a multi-country study in Europe. Presented at ISPOR EU, Barcelona, Spain (2018). https://tools.ispor.org/research_pdfs/60/pdffiles/PHP113.pdf
- 33. Biosimilar switching - current state of knowledge. Reumatologia 56(4), 234–242 (2018).
- 34. EMA. Biosimilars in the EU (2019) www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf
- 35. . Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. Drugs 78(4), 463–478 (2018).
- 36. . Can we continue to afford access to cancer treatment? Eur. Oncol. Haematol. 13(2), 114–119 (2017). • A concise summary of the growing issues with maintaining the sustainability of cancer treatment.
- 37. . What happens when the cost of cancer care becomes unsustainable? Eur. Oncol. Haematol. 13(2), 108–113 (2017).
- 38. . Potential solutions for sustaining the costs of cancer drugs. Eur. Oncol. Haematol. 13(2), 102–107 (2017). • An elegant overview of potential solutions to issues of sustainability in cancer care, of which biosimilars represent one avenue.
- 39. . Subcutaneous versus intravenous rituximab in non-hodgkin lymphoma treated with R-CHOP: economic modeling for the US (ASH 2018 abstract). Blood 132, 4776 (2018).
- 40. . The economic impact of biosimilars in oncology and hematology: the case of trastuzumab and rituximab. Anticancer Res. 39(7), 3971–3973 (2019).