On 2017 Jun 19, Daniele Mengato commented:

Rituximab biosimilar vs rituximab originator in advanced follicular lymphoma

by Daniele Mengato Scuola di Specializzazione in Farmacia Ospedaliera, Dipartimento di Scienze del Farmaco, University of Padua, Padova, Italy

One interesting point of this article by Gao et al. (1) is that the authors have presented a meta-analysis based on the end-point of the overall response rate in which chemotherapy plus rituximab has been compared with chemotherapy alone in patients with advanced follicular lymphoma (AFL). Schulz et al. (2) have conducted a meta-analysis (published in 2007) based on a similar design. In particular, they used the same endpoint obtained from the same RCTs citated in the work by Gao et al. EMA has recently approved a biosimilar of rituximab (called CPT-10) indicated for patients with AFL (3). In documenting the equivalence between CPT-10 and the originator of rituximab, the analysis carried out by EMA has evaluated the randomized trial that directly compared these two agents in the above-mentioned patients. Clinical endpoint investigated in this trial was the same as the one used in the already mentioned meta-analysis: the overall response rate. It has been proposed (4) that an analysis focused on the equivalence between a biosimilar and an originator can be strengthened if a network meta-analysis is performed that includes not only the comparison between biosimilar and originator, but also the comparison between the originator and the old standard of care (i.e. chemotherapy alone). We welcome one such network meta-analysis. For this purpose, as regards the comparison between the originator plus chemotherapy and chemotherapy alone, the 6 trials (5-10) either reported by Gao et al. or by Schulz et al. are suitable for being included in this network meta-analysis.

References

1. Gao G, Liang X, Jiang J, Zhou X, et al. A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma. Acta oncologica. 2010 Jan;49(1):3-12.
2. Schulz H, Bohlius J, Skoetz N, et al. Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma. The Cochrane database of systematic reviews. 2007 Oct 17(4):Cd003805.
3. EMA European Medicine Agency - Committee for Medicinal Products for Human Use (CHMP). Truxima : EPAR - Public assessment report. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004112/WC500222695.pdf 2016 May;EMA/CHMP/75695/2017
4. Messori A, Trippoli S, Marinai C. Network meta-analysis as a tool for improving the effectiveness assessment of biosimilars based on both direct and indirect evidence: application to infliximab in rheumatoid arthritis. Eur J Clin Pharmacol. 2017 Apr;73(4):513-514. doi:10.1007/s00228-016-2177-z. Epub 2016 Dec 14.
5. Forstpointer R, Dreyling M, Repp R, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004;104(10):3064-3071.
6. Herold M, Pasold R, Srock S, et al. Results of a Prospective Randomised Open Label Phase III Study Comparing Rituximab Plus Mitoxantrone, Chlorambucile, Prednisolone Chemotherapy (R-MCP) Versus MCP Alone in Untreated Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) and MantleCell-Lymphoma (MCL). ASH Annual Meeting Abstracts. 2004; Vol. 104, issue 11:584.
7. Hiddemann W, Kneba B, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005;106(12):3725–3732.
8. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105(4):1417–1423.
9. Rivas-Vera S, Baez E, Sobrevilla-Calvo P, et al. Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP. ASH Annual Meeting Abstracts. 2005; Vol. 106, issue 11:2431.
10. van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial.. Blood 2006;108 (10):3295–301.

On 2017 Jun 19, Daniele Mengato commented:

Rituximab biosimilar vs rituximab originator in advanced follicular lymphoma

by Daniele Mengato Scuola di Specializzazione in Farmacia Ospedaliera, Dipartimento di Scienze del Farmaco, University of Padua, Padova, Italy

One interesting point of this article by Gao et al. (1) is that the authors have presented a meta-analysis based on the end-point of the overall response rate in which chemotherapy plus rituximab has been compared with chemotherapy alone in patients with advanced follicular lymphoma (AFL). Schulz et al. (2) have conducted a meta-analysis (published in 2007) based on a similar design. In particular, they used the same endpoint obtained from the same RCTs citated in the work by Gao et al. EMA has recently approved a biosimilar of rituximab (called CPT-10) indicated for patients with AFL (3). In documenting the equivalence between CPT-10 and the originator of rituximab, the analysis carried out by EMA has evaluated the randomized trial that directly compared these two agents in the above-mentioned patients. Clinical endpoint investigated in this trial was the same as the one used in the already mentioned meta-analysis: the overall response rate. It has been proposed (4) that an analysis focused on the equivalence between a biosimilar and an originator can be strengthened if a network meta-analysis is performed that includes not only the comparison between biosimilar and originator, but also the comparison between the originator and the old standard of care (i.e. chemotherapy alone). We welcome one such network meta-analysis. For this purpose, as regards the comparison between the originator plus chemotherapy and chemotherapy alone, the 6 trials (5-10) either reported by Gao et al. or by Schulz et al. are suitable for being included in this network meta-analysis.

References

1. Gao G, Liang X, Jiang J, Zhou X, et al. A systematic review and meta-analysis of immunochemotherapy with rituximab for B-cell non-Hodgkin's lymphoma. Acta oncologica. 2010 Jan;49(1):3-12.
2. Schulz H, Bohlius J, Skoetz N, et al. Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma. The Cochrane database of systematic reviews. 2007 Oct 17(4):Cd003805.
3. EMA European Medicine Agency - Committee for Medicinal Products for Human Use (CHMP). Truxima : EPAR - Public assessment report. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/004112/WC500222695.pdf 2016 May;EMA/CHMP/75695/2017
4. Messori A, Trippoli S, Marinai C. Network meta-analysis as a tool for improving the effectiveness assessment of biosimilars based on both direct and indirect evidence: application to infliximab in rheumatoid arthritis. Eur J Clin Pharmacol. 2017 Apr;73(4):513-514. doi:10.1007/s00228-016-2177-z. Epub 2016 Dec 14.
5. Forstpointer R, Dreyling M, Repp R, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004;104(10):3064-3071.
6. Herold M, Pasold R, Srock S, et al. Results of a Prospective Randomised Open Label Phase III Study Comparing Rituximab Plus Mitoxantrone, Chlorambucile, Prednisolone Chemotherapy (R-MCP) Versus MCP Alone in Untreated Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) and MantleCell-Lymphoma (MCL). ASH Annual Meeting Abstracts. 2004; Vol. 104, issue 11:584.
7. Hiddemann W, Kneba B, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005;106(12):3725–3732.
8. Marcus R, Imrie K, Belch A, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105(4):1417–1423.
9. Rivas-Vera S, Baez E, Sobrevilla-Calvo P, et al. Is First Line Single Agent Rituximab the Best Treatment for Indolent Non-Hodgkin’s Lymphoma? Update of a Multicentric Study Comparing Rituximab vs CNOP vs Rituximab Plus CNOP. ASH Annual Meeting Abstracts. 2005; Vol. 106, issue 11:2431.
10. van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial.. Blood 2006;108 (10):3295–301.