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A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia

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Abstract

Novel therapies are needed for children with relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). Blinatumomab is a bispecific T-cell engager immunotherapy that simultaneously binds to CD3-positive cytotoxic T cells and CD19-positive B cells and redirects the patient’s T cells to lyse malignant and normal B cells. We conducted an open-label phase 1b study to determine the safety, pharmacokinetics, efficacy, and recommended dose of blinatumomab in Japanese children with R/R B-cell precursor ALL. Patients received induction blinatumomab for 4 weeks (5 μg/m2/day week 1; 15 μg/m2/day weeks 2–4), followed by a 2-week treatment-free interval (6-week cycle). In subsequent cycles, patients received blinatumomab 15 μg/m2/day. The primary end point was the incidence of dose-limiting toxicities. Nine patients received blinatumomab. Since no dose-limiting toxicities were reported, the maximum tolerated dose was 5 μg/m2/day for week 1, followed by 15 μg/m2/day weeks 2–4 (5–15 μg/m2/day, the global recommended dose of blinatumomab). All patients had ≥ 1 grade ≥ 3 adverse events; 89% had grade ≥ 3 treatment-related adverse events. M1 remission rate within the first two cycles of treatment was 56%; one patient had a minimal residual disease response. Consistent with global studies, blinatumomab appeared to be safe with preliminary evidence of efficacy in Japanese children with R/R B-cell precursor ALL.

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Acknowledgements

Writing support was funded by Amgen Inc. and was provided by Kathryn Boorer, PhD, of KB Scientific Communications, LLC. The authors would like to thank Min Zhu for assistance with the pharmacokinetic analysis.

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Authors and Affiliations

  1. Department of Pediatrics, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan

    Keizo Horibe

  2. Clinical Development, Amgen Inc., Thousand Oaks, CA, USA

    Joan D. Morris

  3. Global Biostatistical Science, Amgen Inc., Thousand Oaks, CA, USA

    Catherine A. Tuglus

  4. Clinical Biomarkers, Amgen Inc., South San Francisco, CA, USA

    Cedric Dos Santos

  5. Clinical Pharmacology, Amgen Inc., South San Francisco, CA, USA

    James Kalabus

  6. Clinical Biomarkers, Amgen Inc., Thousand Oaks, CA, USA

    Abraham Anderson

  7. Division of Hematology/Oncology, Kanagawa Children’s Medical Center, Yokohama, Kanagawa, Japan

    Hiroaki Goto

  8. Department of Pediatric Oncology, National Cancer Center Hospital, Chūō, Tokyo, Japan

    Chitose Ogawa

Authors
  1. Keizo Horibe
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  2. Joan D. Morris
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  3. Catherine A. Tuglus
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  4. Cedric Dos Santos
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  5. James Kalabus
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  6. Abraham Anderson
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  7. Hiroaki Goto
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  8. Chitose Ogawa
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Contributions

Study conception and design: JDM, CO, HG. Data collection and analysis were performed by: KH, CDS, JK, AA, CAT. Manuscript drafts were written and reviewed by all authors. The funder contributed to study design, data collection, data analysis, and data interpretation, and funded a professional medical writer to assist with writing the report. The authors had full access to all data in the study and had final responsibility for the decision to submit for publication.

Corresponding author

Correspondence to Keizo Horibe.

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Conflict of interest

This clinical trial was funded by Amgen Inc. and Amgen Astellas BioPharma K. K. (ClinicalTrials.gov: NCT02412306). KH, HG, and CO are advisory board members of Amgen Inc. JDM, CAT, and AA are employees and stockholders of Amgen Inc. CDS and JK are former employees and stockholders of Amgen Inc.

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Horibe, K., Morris, J.D., Tuglus, C.A. et al. A phase 1b study of blinatumomab in Japanese children with relapsed/refractory B-cell precursor acute lymphoblastic leukemia. Int J Hematol 112, 223–233 (2020). https://doi.org/10.1007/s12185-020-02907-9

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  • DOI: https://doi.org/10.1007/s12185-020-02907-9

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