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International Journal of Hematology

, Volume 109, Issue 6, pp 657–664 | Cite as

A multicenter phase I study of inebilizumab, a humanized anti-CD19 monoclonal antibody, in Japanese patients with relapsed or refractory B-cell lymphoma and multiple myeloma

  • Ken OhmachiEmail author
  • Michinori Ogura
  • Youko Suehiro
  • Kiyoshi Ando
  • Toshiki Uchida
  • Ilseung Choi
  • Yoshiaki Ogawa
  • Miki Kobayashi
  • Koichi Fukino
  • Yuki Yokoi
  • Jun Okamura
Original Article

Abstract

This multicenter, phase I, open-label dose escalation study evaluated safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of inebilizumab in Japanese patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), or multiple myeloma (MM) who were ineligible for hematopoietic stem cell transplantation. Patients received inebilizumab 2, 4, or 8 mg/kg intravenously on days 1 and 8 of the first 28-day cycle, and once every 28 days thereafter, with a 12 mg/kg cohort added. Twenty patients (11 FL, six DLBCL, two CLL, and one MM) received inebilizumab at four dose levels (2 mg/kg cohort, n = 3; 4 mg/kg cohort, n = 7; 8 mg/kg cohort, n = 4; 12 mg/kg cohort, n = 6). Three patients experienced dose-limiting toxicities: grade 4 neutropenia/grade 3 leukopenia (n = 1, 12 mg/kg) and grade 3 infusion reaction (n = 1 each, 4 mg/kg and 12 mg/kg); the maximum tolerated dose was 8 mg/kg. Four (three FL and one DLBCL) patients achieved complete response; eight (six FL and two DLBCL) achieved partial response. Overall response rate was 60%. Over the dose ranges evaluated, the pharmacokinetic profile of inebilizumab in Japanese patients was generally dose proportional. This phase I study showed acceptable toxicity and preliminary and promising efficacy of inebilizumab in patients with relapsed/refractory FL and DLBCL.

Keywords

Asian B-cell chronic lymphocytic leukemia Follicular lymphoma Malignancy Pharmacokinetics 

Notes

Acknowledgements

The authors thank the patients who participated in this study and their families. We also thank all the investigators, nursing staff, and research support staff who contributed to the study. Medical writing and editorial support were provided by Amy Zannikos, PharmD, of Peloton Advantage (Parsippany, NJ) and funded by MedImmune, the global biologics R&D arm of AstraZeneca.

Compliance with ethical standards

Conflict of interest

K.O., M.O., Y.S., K.A., T.U., I.C., Y.O., M.K. and J.O. have received research Grants from AstraZeneca. K.F. was an employee of AstraZeneca and owned stock/stock options in the company at the time of the study. Y.Y. is an employee of AstraZeneca and owns stock/stock options in the company. This study was designed under the responsibility of MedImmune, the global biologics R&D arm of AstraZeneca, the study was funded by MedImmune, and the study drug was provided by MedImmune. Each author had full access to the data, made substantial contributions to the drafting and/or revision of this manuscript, and granted approval for the submission of this paper. No author received an honorarium or other form of financial support related to the development of this manuscript.

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Copyright information

© Japanese Society of Hematology 2019

Authors and Affiliations

  • Ken Ohmachi
    • 1
    Email author
  • Michinori Ogura
    • 2
    • 3
  • Youko Suehiro
    • 4
  • Kiyoshi Ando
    • 1
  • Toshiki Uchida
    • 3
  • Ilseung Choi
    • 4
  • Yoshiaki Ogawa
    • 1
  • Miki Kobayashi
    • 3
  • Koichi Fukino
    • 5
    • 6
  • Yuki Yokoi
    • 5
  • Jun Okamura
    • 4
  1. 1.Department of Hematology and Oncology, Tokai University HospitalTokai University School of MedicineIseharaJapan
  2. 2.Kasugai Municipal HospitalKasugaiJapan
  3. 3.Department of Hematology and OncologyJapanese Red Cross Nagoya Daini HospitalNagoyaJapan
  4. 4.Department of HematologyNational Hospital Organization Kyushu Cancer CenterFukuokaJapan
  5. 5.AstraZeneca K.K.OsakaJapan
  6. 6.Clinical DevelopmentAllergan Japan K.K.TokyoJapan

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