Skip to main content
Log in

A novel rituximab administration protocol to minimize infusion-related adverse reactions in patients with B-cell lymphoma

  • Research Article
  • Published:
International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background Infusion-related reactions (IRRs) during rituximab administration are occasionally severe and remain problematic in oncology practice. Aim To establish a safer, risk-stratified rituximab protocol for patients with B-cell lymphoma. Method We stratified patients into low-, moderate-, and high-risk groups according to the number of risk factors for IRRs, specifically, low-grade histology and bulky tumors (> 10 cm): Then, the administrating schedule of rituximab (375 mg/m2, diluted in 1 mg/mL concentration) was individualized. For the first rituximab cycle, the low- and moderate-risk groups underwent conventional infusion #1 (25–200 mg/h, ~4.3 h), and the high-risk group underwent long infusion (25–100 mg/h, 6.8 h). Patients in the low-, moderate-, and high-risk groups without IRRs in the first cycle underwent short infusion (100–400 mg/h, 2.3 h), conventional infusion #2 (100–200 mg/h, 3.5 h), and conventional infusion #1, respectively. Patients with IRRs in the first cycle received a second rituximab cycle with the same schedule as the first cycle. The procedure for the third cycle was at the attending physician’s discretion. Results Among 81 patients, the overall incidence of IRRs was 28%. IRR incidences in the low- (n = 39), moderate- (n = 35), and high-risk groups (n = 7) were 31%, 20%, and 57%, respectively. All IRRs were grade ≤ 2. The overall conversion rate to short infusion in the third cycle was 54%, without any IRRs. Conclusions Our step-by-step rituximab protocol demonstrated a fewer incidence of severe IRRs among B-cell lymphoma patients receiving rituximab.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Salles G, Barrett M, Foà R, Maurer J, O’Brien S, Valente N et al. Rituximab in B-Cell hematologic malignancies: a review of 20 years of clinical experience. Adv Ther. 2017;34:2232–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Paul F, Cartron G. Infusion-related reactions to rituximab: frequency, mechanisms and predictors. Expert Rev Clin Immunol 2019;15:383–9.

    Article  CAS  PubMed  Google Scholar 

  3. Jung JW, Kang HR, Lee SH, Cho SH. The incidence and risk factors of infusion-related reactions to rituximab for treating B cell malignancies in a single tertiary hospital. Oncologist 2014;86:127–34.

    Article  CAS  Google Scholar 

  4. D’Arena G, Simeon V, Laurenti L, Cimminiello M,  Innocenti I, Gilio M, et al. Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicent. Leuk Lymphoma 2017;58:2633–41.

    Article  PubMed  Google Scholar 

  5. Schwartzberg LS, Stepanski EJ, Walker MS, Mathias S, Houts AC, Fortner BV. Implications of IV monoclonal antibody infusion reaction for the patient, caregiver, and practice: results of a multicenter study. Support Care Cancer. 2009;17:91–8.

    Article  PubMed  Google Scholar 

  6. Schwartzberg LS, Stepanski EJ, Fortner BV, Houts AC. Retrospective chart review of severe infusion reactions with rituximab, cetuximab, and bevacizumab in community oncology practices: assessment of clinical consequences. Support Care Cancer 2008;16:393–8.

    Article  PubMed  Google Scholar 

  7. Vogel H W. Infusion reactions: diagnosis, assessment, and management. Clin J Oncol Nurs 2010;14:E10–21.

    Article  PubMed  Google Scholar 

  8. Hayama T, Miura K, Uchiike A, Nakagawa M, Tsutsumi D, Sakagami M, et al. A clinical prediction model for infusion-related reactions to rituximab in patients with B cell lymphomas. Int J Clin Pharm 2017;39:380–5.

    Article  CAS  PubMed  Google Scholar 

  9. Chung CH. Managing premedications and the risk for reactions to infusional monoclonal antibody therapy. Oncologist 2008;13:725–32.

    Article  CAS  PubMed  Google Scholar 

  10. Common terminology criteria for adverse events. 2010. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/. Accessed on 10 Sept 2021.

  11. Jung JW, Kang HR, Lee SH, Cho SH. The incidence and risk factors of infusion-related reactions to rituximab for treating B cell malignancies in a single tertiary hospital. Oncology. 2014;86:127–134.

    Article  CAS  PubMed  Google Scholar 

  12. Atmar J. Review of the safety and feasibility of rapid infusion of rituximab. J Oncol Pract 2010;6:91–3.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Provencio M, Cerdeira S, Bonilla F, Sánchez A, España P. Rapid-infusion rituximab in lymphoma treatment. Ann Oncol 2006;17:1027–8.

    Article  CAS  PubMed  Google Scholar 

  14. Lang DS, Keefe DM, Schultz T, Pearson A. Predictors of acute adverse events from rapid rituximab infusion. Support Care Cancer 2013;21:2315–20.

    Article  PubMed  Google Scholar 

  15. Dakhil S, Hermann R, Schreeder MT, Gregory SA, Monte M, Windsor KS, et al. Phase III safety study of rituximab administered as a 90-minute infusion in patients with previously untreated diffuse large B-cell and follicular lymphoma. Leuk Lymphoma 2014;55:2335–40.

    Article  CAS  PubMed  Google Scholar 

  16. Courville J, Nastoupil L, Kaila N, Kelton J, Zhang J, Alcasid A, et al. Factors influencing infusion-related reactions following dosing of reference rituximab and PF-05280586, a rituximab biosimilar. BioDrugs. 2021;35:459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Sharman JP, Liberati AM, Ishizawa K, Khan T, Robbins J, Alcasid A, et al. A randomized, double-blind, efficacy and safety study of PF-05280586 (a rituximab biosimilar) compared with rituximab reference product (MabThera®) in subjects with previously untreated CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL). BioDrugs 2020;34:171–81.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Mr. I. Odagiri, Mr. T. Yamauchi, Dr. H. Takahashi, Dr. M. Nakagawa, Dr. Y. Uchino, Dr. K. Iizuka, Dr. T. Hamada, and Dr. N. Iriyama for their enormous contributions to this work.

Funding

This study was not funded by any third parties.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Katsuhiro Miura.

Ethics declarations

Conflicts of interest

K. M. and Y. H. received speaker fees from Chugai and Kyowa-Kirin, which manufactures rituximab and its biosimilar products in Japan. The other authors have no conflicts of interest to disclose.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This study was registered in UMIN-CTR (https://www.umin.ac.jp/english/) on 19th April 2018 (Registration ID: UMIN000032309).

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 117 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsutsumi, D., Hayama, T., Miura, K. et al. A novel rituximab administration protocol to minimize infusion-related adverse reactions in patients with B-cell lymphoma. Int J Clin Pharm 44, 366–373 (2022). https://doi.org/10.1007/s11096-021-01348-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11096-021-01348-6

Keywords

Navigation