Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Potential niche indications for blinatumomab as a bridge to hematopoietic cell transplantation

Bone Marrow Transplantation volume 52, pages 1671–1673 (2017)Cite this article

Subjects

Blinatumomab, a bispecific monoclonal Ab that directs CD3+ T cells to lyse CD19+ leukemic blasts, has been shown to achieve minimal residual disease (MRD)-negative remissions in adult and pediatric patients with relapsed or refractory pre-B ALL, even after hematopoietic cell transplant (HCT).1, 2, 3, 4, 5, 6, 7, 8 However, reports of blinatumomab as a bridge therapy for HCT in pediatric patients with relapsed/refractory ALL remain limited.1, 5, 8 Our experience in treating relapsed or refractory pediatric ALL is that blinatumomab is an efficacious and well-tolerated therapy that induces molecular MRD in heavily pre-treated patients, allowing them to proceed to allogeneic HCT with good organ function, excellent performance status and free of opportunistic infections.

From April 2015 through November 2016, five patients aged between 2 and 20 years with relapsed or refractory ALL were treated with blinatumomab as a continuous infusion at 15 μg/m2/day for 28 days per cycle. All patients achieved MRD-negative CR following blinatumomab and proceeded to myeloablative HCT. They all remain disease-free 9–19 months post HCT (Table 1). Local IRB approval was obtained to review and report these findings. We concentrate our discussion on three of the patients (patients nos. 3, 4 and 5, Table 1) that illustrate clear advantages of blinatumomab over other available therapeutic options for relapsed/refractory ALL.

Table 1 Patient data
Full size table

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

References

  1. Handgretinger R, Zugmaier G, Henze G, Kreyenberg H, Lang P, von Stackelberg A . Complete remission after blinatumomab-induced donor T-cell activation in three pediatric patients with post-transplant relapsed acute lymphoblastic leukemia. Leukemia 2011; 25: 181–184.

    Article  CAS  Google Scholar 

  2. Kantarjian H, Stein A, Gokbuget N, Fielding AK, Schuh AC, Ribera JM et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017; 376: 836–847.

    Article  CAS  Google Scholar 

  3. Loffler A, Kufer P, Lutterbuse R, Zettl F, Daniel PT, Schwenkenbecher JM et al. A recombinant bispecific single-chain antibody, CD19 × CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 2000; 95: 2098–2103.

    CAS  PubMed  Google Scholar 

  4. Mack M, Riethmuller G, Kufer P . A small bispecific antibody construct expressed as a functional single-chain molecule with high tumor cell cytotoxicity. Proc Natl Acad Sci USA 1995; 92: 7021–7025.

    Article  CAS  Google Scholar 

  5. Schlegel P, Lang P, Zugmaier G, Ebinger M, Kreyenberg H, Witte KE et al. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99: 1212–1219.

    Article  Google Scholar 

  6. Topp MS, Gokbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC et al. 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 2015; 16: 57–66.

    Article  CAS  Google Scholar 

  7. Topp MS, Gokbuget N, Zugmaier G, Klappers P, Stelljes M, Neumann S et al. 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 2014; 32: 4134–4140.

    Article  CAS  Google Scholar 

  8. von Stackelberg A, Locatelli F, Zugmaier G, Handgretinger R, Trippett TM, Rizzari C et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol 2016; 34: 4381–4389.

    Article  CAS  Google Scholar 

  9. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371: 1507–1517.

    Article  Google Scholar 

  10. Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014; 6: 224ra25.

    Article  Google Scholar 

  11. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385: 517–528.

    Article  CAS  Google Scholar 

  12. Martinelli G, Boissel N, Chevallier P, Ottmann O, Gokbuget N, Topp MS et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol 2017; 5: 1795–1802.

    Article  Google Scholar 

Download references

Acknowledgements

We thank all providers at Pediatric Hematology/Oncology/BMT division at the Department of Pediatrics, University of Arizona, for their excellent patient care and Vanessa Frisinger for administrative assistance.

Author contributions

YZ and EK collected the data and wrote the manuscript.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Arizona, Tucson, Arizona, USA

    Yi Zeng & Emmanuel Katsanis

  2. University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA

    Yi Zeng & Emmanuel Katsanis

  3. Banner University Medical Center, Tucson, Arizona, USA

    Yi Zeng & Emmanuel Katsanis

  4. Department of Immunobiology, Tucson, Arizona, USA

    Emmanuel Katsanis

  5. Department of Medicine, Tucson, Arizona, USA

    Emmanuel Katsanis

  6. Department of Pathology, Tucson, Arizona, USA

    Emmanuel Katsanis

Authors
  1. Yi Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Emmanuel Katsanis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Emmanuel Katsanis.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zeng, Y., Katsanis, E. Potential niche indications for blinatumomab as a bridge to hematopoietic cell transplantation. Bone Marrow Transplant 52, 1671–1673 (2017). https://doi.org/10.1038/bmt.2017.186

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2017.186

Search

Advanced search

Quick links