Skip to main content

Advertisement

SpringerLink
Log in

Pretreatment blast-to-lymphocyte ratio as a prognostic marker for CD19/CD3-bispecific T cell-engaging antibodies (blinatumomab) treatment against relapsed or refractory B-precursor acute lymphoblastic leukemia

  • Brief Report
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Blinatumomab is an immunotherapy drug approved for the treatment of acute lymphoblastic leukemia. Since not all patients respond to blinatumomab, markers are needed to predict the efficacy of blinatumomab in individual patients. We hypothesized that the pre-treatment blast-to-lymphocyte ratio would predict blinatumomab efficacy. To examine this possibility, we conducted a post hoc analysis using data from the TOWER Clinical Trials (NCT02013167). Multivariate analysis showed that, along with the treatment groups, each of the following was independently correlated with superior progression-free survival: salvage-treatment phase, allogeneic stem cell transplantation, and pre-treatment ratio of bone marrow blasts-to-peripheral blood lymphocytes < 25.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The data belongs to AMGEN and provided though Clinical Trail Data and Document Sharing Request.

References

  1. Löffler A, Gruen M, Wuchter C et al (2003) Efficient elimination of chronic lymphocytic leukaemia B cells by autologous T cells with a bispecific anti-CD19/anti-CD3 single-chain antibody construct. Leukemia 17:900–909. https://doi.org/10.1038/sj.leu.2402890

    Article  CAS  PubMed  Google Scholar 

  2. Dreier T, Lorenczewski G, Brandl C et al (2002) Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int J Cancer 100:690–697. https://doi.org/10.1002/ijc.10557

    Article  CAS  PubMed  Google Scholar 

  3. Hoffmann P, Hofmeister R, Brischwein K et al (2005) Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int J Cancer 115:98–104. https://doi.org/10.1002/ijc.20908

    Article  CAS  PubMed  Google Scholar 

  4. Brandl C, Haas C, D’Argouges S et al (2007) The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct. Cancer Immunol Immunother 56:1551–1563. https://doi.org/10.1007/s00262-007-0298-z

    Article  CAS  PubMed  Google Scholar 

  5. Huo Y, Sheng Z, Lu DR et al (2021) Blinatumomab-induced T cell activation at single cell transcriptome resolution. BMC Genomics 22:1–16. https://doi.org/10.1186/s12864-021-07435-2

    Article  CAS  Google Scholar 

  6. Löffler A, Kufer P, Lutterbüse R et al (2000) A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95:2098–2103. https://doi.org/10.1182/blood.v95.6.2098

    Article  PubMed  Google Scholar 

  7. Topp MS, Gökbuget N, Zugmaier G et al (2014) Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J Clin Oncol 32:4134–4140. https://doi.org/10.1200/JCO.2014.56.3247

    Article  CAS  PubMed  Google Scholar 

  8. Topp MS, Gökbuget N, Stein AS et al (2015) Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol 16:57–66. https://doi.org/10.1016/S1470-2045(14)71170-2

    Article  CAS  PubMed  Google Scholar 

  9. Kantarjian H, Stein A, Gökbuget N et al (2017) Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 376:836–847. https://doi.org/10.1056/nejmoa1609783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rogala B, Freyer CW, Ontiveros EP et al (2015) Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. Expert Opin Biol Ther 15:895–908. https://doi.org/10.1517/14712598.2015.1041912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wei AH, Ribera JM, Larson RA et al (2021) Biomarkers associated with blinatumomab outcomes in acute lymphoblastic leukemia. Leukemia 35:2220–2231. https://doi.org/10.1038/s41375-020-01089-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shimazu Y, Kanda J, Kaneko H et al (2022) Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide. Ther Adv Hematol. https://doi.org/10.1177/20406207221142487

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shimazu Y, Kanda J, Kosugi S et al (2023) Efficacy of elotuzumab for multiple myeloma in reference to lymphocyte counts and kappa/lambda ratio or B2 microglobulin. Sci Rep 13:5159. https://doi.org/10.1038/S41598-023-32426-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kanda Y (2013) Investigation of the freely available easy-to-use software “EZR” for medical statistics. Bone Marrow Transpl 48:452–458. https://doi.org/10.1038/bmt.2012.244

    Article  CAS  Google Scholar 

Download references

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Yutaka Shimazu, Toshio Kitawaki, Tadakazu Kondo & Akifumi Takaori-Kondo

  2. Department of Hematology, Kobe City Medical Center General Hospital, 2-1-1 Minami-machi, Minatojima, Chuo-ku, Kobe, Hyogo, 650-0047, Japan

    Tadakazu Kondo

Authors
  1. Yutaka Shimazu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Toshio Kitawaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tadakazu Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akifumi Takaori-Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

YS and TK performed the research, analyzed data and wrote the paper; TK and supervised the study and performed writing reviewing.

Corresponding author

Correspondence to Toshio Kitawaki.

Ethics declarations

Conflict of interest

All the other authors have no conflict of interest regarding to this study.

Ethical approval

All procedures performed in this study involving the patient were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The ethical approval was waived by Kyoto University Graduate School and Faculty of Medicine, Ethics Committee institutional because the data was provided as anonymized data and the ad-hoc nature of this study.

Additional information

Publisher's Note

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

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shimazu, Y., Kitawaki, T., Kondo, T. et al. Pretreatment blast-to-lymphocyte ratio as a prognostic marker for CD19/CD3-bispecific T cell-engaging antibodies (blinatumomab) treatment against relapsed or refractory B-precursor acute lymphoblastic leukemia. Cancer Immunol Immunother 72, 3861–3865 (2023). https://doi.org/10.1007/s00262-023-03514-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00262-023-03514-3

Keywords

Search

Navigation