Skip to main content

Advertisement

Log in

Primary prophylaxis with pegfilgrastim during the first cycle of R-CHOP to avoid reduction of dose intensity in elderly patients

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

The long-term effects of pegfilgrastim administered in the first cycle of chemotherapy in day-to-day practice remain unclear. We retrospectively identified 114 patients aged ≥ 70 years with diffuse large B-cell lymphoma who received a rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP) regimen in our institution. Twenty-six patients received pegfilgrastim (pegfilgrastim group); of the 88 patients scheduled to receive conventional granulocyte-colony stimulating factor (G-CSF) when their neutrophil count decreased (neut-adjusted-G group), conventional G-CSF was ultimately administered to 57. During the first cycle of R-CHOP, the incidence of febrile neutropenia was lower in the pegfilgrastim group than in the neut-adjusted-G group (0% vs. 18%, p = 0.020). Throughout all cycles, a higher proportion of patients exhibited sustained relative dose intensity (≥ 80%) in the pegfilgrastim group than in the neut-adjusted-G group (25% vs. 4.0%, p = 0.008). A lower proportion of patients received a reduced dose in the second cycle in the pegfilgrastim group than in the neut-adjusted-G group (0% vs. 10%, p = 0.116). Although the differences were not significant, the pegfilgrastim group showed higher progression-free survival and overall survival than the neut-adjusted-G group. Adequate prevention of febrile neutropenia using pegfilgrastim during the first cycle of R-CHOP may contribute to avoidance of dose intensity reduction in all cycles.

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

Similar content being viewed by others

References

  1. Liu Y, Barta SK. Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019;94(5):604–16.

    Article  CAS  PubMed  Google Scholar 

  2. Westin EH, Longo DL. Lymphoma and myeloma in older patients. Semin Oncol. 2004;31(2):198–205.

    Article  PubMed  Google Scholar 

  3. Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(4):235–42.

    Article  CAS  PubMed  Google Scholar 

  4. Lyman GH, Poniewierski MS, Culakova E. Risk of chemotherapy-induced neutropenic complications when treating patients with non-Hodgkin lymphomas. Expert Opin Drug Saf. 2016;15(4):483–92.

    Article  CAS  PubMed  Google Scholar 

  5. Yamaguchi H, Hirakawa T, Inokuchi K. Importance of relative dose intensity in chemotherapy for diffuse large B-cell lymphoma. J Clin Exp Hematopathol. 2011;51(1):1–5.

    Article  Google Scholar 

  6. Yamamoto M, Suzuki I, Saitou K, Tsumanuma R, Okuyama S, Kumagai H, et al. Impact of comorbidity and relative dose intensity on outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP. J Cancer Res Clin Oncol. 2020;146(11):2995–3002.

    Article  CAS  PubMed  Google Scholar 

  7. Wildiers H, Reiser M. Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer on aggressive lymphoma. Crit Rev Oncol Hematol. 2011;77(3):221–40.

    Article  PubMed  Google Scholar 

  8. Holmes FA, Jones SE, O’Shaughnessy J, Vukelja S, George T, Savin M, et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann Oncol. 2002;13(6):903–9.

    Article  CAS  PubMed  Google Scholar 

  9. Tai E, Guy GP, Dunbar A, Richardson LC. Cost of cancer-related neutropenia or fever hospitalizations, United States, 2012. J Oncol Pract. 2017;13(6):e552-561.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in Neutropenia. J Immunol. 2015;195(4):1341–9.

    Article  CAS  PubMed  Google Scholar 

  11. Crawford J, Becker PS, Armitage JO, Blayney DW, Chavez J, Curtin P, et al. Myeloid growth factors, Version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2017;15(12):1520–41.

    Article  CAS  Google Scholar 

  12. Yokoyama M, Kusano Y, Nishihara A, Inoue N, Nishimura N, Mishima Y, et al. Incidence and risk factors for febrile neutropenia in Japanese patients with non-Hodgkin B cell lymphoma receiving R-CHOP: 2-year experience in a single center (STOP FN in NHL 2). Support Care Cancer. 2020;28(2):571–9.

    Article  PubMed  Google Scholar 

  13. Almenar D, Mayans J, Juan O, Bueno JM, Lopez JI, Frau A, et al. Pegfilgrastim and daily granulocyte colony-stimulating factor: patterns of use and neutropenia-related outcomes in cancer patients in Spain-results of the learn study. Eur J cancer Care. 2009;18(3):280–6.

    Article  CAS  Google Scholar 

  14. Matsuda K, Taisuke J, Miyauchi M, Toyama K, Nakazaki K, Matsui H, et al. Primary prophylaxis with pegfilgrastim in patients with newly-diagnosed diffuse large B-cell lymphoma: propensity score and instrumental variable analyses. Leuk Lymphoma. 2020;61(10):2435–41.

    Article  CAS  PubMed  Google Scholar 

  15. Hirakawa T, Yamaguchi H, Yokose N, Gomi S, Inokuchi K, Dan K. Importance of maintaining the relative dose intensity of CHOP-like regimens combined with rituximab in patients with diffuse large B-cell lymphoma. Ann Hematol. 2010;89(9):897–904.

    Article  CAS  PubMed  Google Scholar 

  16. Lyman GH, Dale DC, Crawford J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: a nationwide study of community practices. J Clin Oncol. 2003;21(24):4524–31.

    Article  PubMed  Google Scholar 

  17. Crawford J, Dale DC, Kuderer NM, Culakova E, Poniewierski MS, Wolff D, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J Natl Compr Canc Netw. 2008;6(2):109–18.

    Article  PubMed  Google Scholar 

  18. Vogel CL, Wojtukiewicz MZ, Carroll RR, Tjulandin SA, Barajas-Figueroa LJ, Wiens BL, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol. 2005;23(6):1178–84.

    Article  CAS  PubMed  Google Scholar 

  19. Culakova E, Thota R, Poniewierski MS, Kuderer NM, Wogu AF, Dale DC, et al. Patterns of chemotherapy-associated toxicity and supportive care in US oncology practice: a nationwide prospective cohort study. Cancer Med. 2014;3(2):434–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chan A, Lee CP, Chiang J, Ng R. Breakthrough febrile neutropenia and associated complications among elderly cancer patients receiving myelosuppressive chemotherapy for solid tumors and lymphomas. Support Care Cancer. 2013;21(8):2137–43.

    Article  PubMed  Google Scholar 

  21. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med. 1987;317(17):1098.

    CAS  PubMed  Google Scholar 

  22. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013;48(3):452–8.

    Article  CAS  PubMed  Google Scholar 

  23. Lyman GH, Morrison VA, Dale DC, Crawford J, Delgado DJ, Fridman M, et al. Risk of febrile neutropenia among patients with intermediate-grade non-Hodgkin’s lymphoma receiving CHOP chemotherapy. Leuk Lymphoma. 2003;44(12):2069–76.

    Article  CAS  PubMed  Google Scholar 

  24. Vose JM, Crump M, Lazarus H, Emmanouilides C, Schenkein D, Moore J, et al. Randomized, multicenter, open-label study of pegfilgrastim compared with daily filgrastim after chemotherapy for lymphoma. J Clin Oncol. 2003;21(3):514–9.

    Article  CAS  PubMed  Google Scholar 

  25. Grigg A, Solal-Celigny P, Hoskin P, Taylor K, McMillan A, Forstpointner R, et al. Open-label, randomized study of pegfilgrastim vs daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkin’s lymphoma. Leuk Lymphoma. 2003;44(9):1503–8.

    Article  CAS  PubMed  Google Scholar 

  26. Kubo K, Miyazaki Y, Murayama T, Shimazaki R, Usui N, Urabe A, et al. A randomized, double blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma. Br J Haematol. 2016;174(4):563–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Smith TJ, Bohlke K, Lyman GH, Carson KR, Crawford J, Cross SJ, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33(28):3199–212.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors would like to thank medical affairs division of the University of Tokyo hospital for calculating medical costs, Editage (www.editage.com) for English language editing.

Author information

Authors and Affiliations

Authors

Contributions

MI and KM designed the research. KM, AS, YM and MK advised the research design and analyses. MI collected the patient’s data and analyzed the data. MI and KM wrote the paper. All authors revised the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Mineo Kurokawa.

Ethics declarations

Conflict of interest

Kensuke Matsuda received the lecture fee from Kyowa Kirin. Arika Shimura received the lecture fee from Eisai. Yosuke Masamoto received the lecture fee from Janssen Pharmaceutical, Otsuka Pharmaceutical, Nihon Pharmaceutical, Nippon Shinyaku, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, Celgene, and Kyowa Kirin. Mineo Kurokawa received the lecture fee from MSD, Astellas, AbbVie, Amgen, Sanwa Chemistry, Shire Japan, Daiichi Sankyo, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Janssen Pharmaceutical, Otsuka Pharmaceutical, Nippon Shinyaku, Eisai, Bioverativ Japan, Ono Pharmaceutical, Celgene, and Kyowa Kirin. Mineo Kurokawa received the research funding from Pfizer, Otsuka Pharmaceutical, Chugai Pharmaceutical, Astellas, Kyowa Kirin, Takeda Pharmaceutical, MSD, Teijin, Eisai, Sumitomo Dainippon Pharma, Nippon Shinyaku, Daiichi Sankyo, Ono Pharmaceutical, and AbbVie. None of these is related to the current study.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1116 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ise, M., Matsuda, K., Shimura, A. et al. Primary prophylaxis with pegfilgrastim during the first cycle of R-CHOP to avoid reduction of dose intensity in elderly patients. Int J Hematol 113, 823–831 (2021). https://doi.org/10.1007/s12185-021-03118-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-021-03118-6

Keywords

Navigation