Abstract
Rituximab is the standard of care for most B-cell malignancies. Its rapid clinical development enabled patients to receive this life-prolonging medicine sooner; however, it precluded a thorough assessment of dose selection. Extensive clinical pharmacology data collected from the recent subcutaneous development program enabled re-examination of this old question and support that the approved rituximab dosing regimens in non-Hodgkin’s lymphoma and chronic lymphocytic leukemia appear to maximize the clinical benefit in the majority of patients.
This is a preview of subscription content, log in via an institution to check access.
References
Salles G, Barrett M, Foa R et al (2017) Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience. Adv Ther 34(10):2232–2273. https://doi.org/10.1007/s12325-017-0612-x. Epub 2017 Oct 5
Davies A, Berge C, Boehnke A et al (2017) Subcutaneous rituximab for the treatment of B-cell hematologic malignancies: a review of the scientific rationale and clinical development. Adv Ther 34(10):2210–2231
Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) Meeting on March 29 (2017) https://www.fda.gov/AdvisoryCommittees/Calendar/ucm547160.htm. Accessed 2 Jan 2019
Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) Meeting on March 29 (2017) Roche Briefing package. https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm547155.htm. Accessed 20 Mar 2019
Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) Meeting on March 29 (2017) FDA Briefing package. https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm547155.htm. Accessed 20 Mar 2019
Li J, Zhi J, Wenger M et al (2012) Population pharmacokinetics of rituximab in patients with chronic lymphocytic leukemia. J Clin Pharmacol 52:1918–1926
Gibiansky E, Gibiansky L, Carlile DJ et al (2014) Population pharmacokinetics of obinutuzumab (GA101) in chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma and exposure-response in CLL. CPT Pharmacomet Syst Pharmacol 29;3:e144. https://doi.org/10.1038/psp.2014.42
Berinstein NL, Grillo-López AJ, White CA et al (1998) Association of serum rituximab (IDECC2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 9(9):995–1001
Gibiansky E, Brewster M, Chavanne C et al (2015) Comparison of population PK and exposure-response relationships of intravenous rituximab and subcutaneous rituximab in patients with CLL. Poster session presented at: 2015 PAGE annual meeting, June 2–5, Hersonissos, Crete, Greece
Dayde D, Ternant D, Ohresser M et al (2009) Tumor burden influences exposure and response to rituximab: pharmacokinetic-pharmacodynamic modeling using a syngeneic bioluminescent murine model expressing human CD20. Blood 113(16):3765–3772. https://doi.org/10.1182/blood-2008-08-175125 (Epub 2008 Nov 24)
Yin A, Li J, Hurst D et al (2010) Population pharmacokinetics (PK) and association of PK and clinical outcomes of rituximab in patients with non-Hodgkin’s lymphoma. J Clin Oncol 28(suppl 15):e13108
Maloney DG, Grillo-López AJ, White CA et al (1997) IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90:2188–2195
Lazzarino M, Arcaini L, Orlandi E et al (2005) Immunochemotherapy with rituximab, vincristine and 5-day cyclophosphamide for heavily pretreated follicular lymphoma. Oncology 68:146–153
Gordan LN, Grow WB, Pusateri A et al (2005) Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol 23:1096–1102
Igarashi T, Kobayashi Y, Ogura M et al (2002) Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study. Ann Oncol 13:928–943
Tobinai K, Igarashi T, Itoh K et al (2004) Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma. Ann Oncol 15:821–830
Jäger U, Fridrick M, Zeitlinger M et al (2012) Rituximab serum concentrations during immunochemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica 97:1431–1438
Kamisoglu K, Phipps A, Jamois C et al (2017) Greater efficacy and potency of obinutuzumab compared with rituximab in chronic lymphocytic leukemia patients confirmed by a semi-mechanistic pharmacokinetic/pharmacodynamic model. Blood 130(Suppl 1):1267. http://www.bloodjournal.org/content/130/Suppl_1/1267. Accessed 2 Jan 2019
Funding
This work was supported by F. Hoffmann-La Roche.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
P. N. Morcos and A. Boehnke are employees of, and own stock/stock options in, Roche. N Valente is an employee of Genentech and own stock/stock options in Roche.
Ethical approval
All procedures performed in clinical studies with human subjects were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards and with the ethical standards of the institutional and/or national research committee.
Informed consent
Informed consent was obtained from all human subjects included in the studies.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Morcos, P.N., Boehnke, A., Valente, N. et al. Rituximab dosing in hematological malignancies: an old question, revisited. Cancer Chemother Pharmacol 84, 661–666 (2019). https://doi.org/10.1007/s00280-019-03818-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00280-019-03818-1